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[(c)-19.7(y)0(t)-19.7(e)-.2(s)-19.7(,)-214.1(a)-19.7(n)0(d)-216.6(h)-19.7(e)-5.8(p)-19.7(at)-19.7(oc)-19.7(yt)-19.7(es)-19.7(,)-214.1(a)-19.7(s)-207.2(w)-19.7(el)-19.7(l)-212.2(a)-19.7(s)-212.9(v)-19.7(as)-19.7(cu)-19.7(la)-19.7(r)-213.1(c)-19.7(el)-19.7(ls)-19.7(,)-214.1(g)-19.7(en)-19.7(er)-19.7(at)-19.7(e)-213.3(R)-19.7(OS)]TJ
0 -1.1116 TD
0 Tc
[(\(6)20.9(0,)-229.2(69)20.8(,)-239.6(7)0(9)20.8(,)-239.6(89)20.8(,)-233.8(1)0(1)15.1(6)0(,)-223.4(1)0(2)20.8(2)0(\))15.1(.)-233.8(Al)19.8(th)15(ou)20.8(gh)-226.8(ma)18.4(ny)-226.8(en)19.7(zy)19.7(ma)18.4(ti)20.6(c)-238.4(s)0(o)15.3(u)0(r)20.9(c)0(e)18.5(s)0(,)]TJ
T*
[(su)21(ch)-170.4(as)-176(mi)19.5(to)20.7(ch)19.7(on)20.8(dr)20.9(ia)13.8(,)-176.2(p)0(e)19.7(r)0(o)15.1(x)0(i)20.7(s)0(o)21(m)0(e)18.4(s)0(,)-171.4(a)0(n)19.7(d)-179.6(cy)19.7(to)20.7(ch)13.9(ro)20.9(me)-171.6(P4)21(50)20.8(,)-182(c)0(a)18.5(n)]TJ
0 -1.1174 TD
[(pr)20.9(od)15.1(uc)19.7(e)-249.9(R)0(O)18.9(S)-248.6(in)-244.2(th)20.7(es)19.9(e)-249.9(c)0(e)18.5(l)0(l)20.6(s)0(,)-240.5(N)0(o)14.2(x)-248.8(is)-238.3(es)14.1(pe)19.7(ci)19.5(al)19.6(ly)-238.5(im)19.5(po)20.8(rt)15(an)19.7(t)-248.9(a)0(s)-239.3(i)0(t)14.8(s)]TJ
0 -1.1116 TD
[(pr)20.9(im)19.5(ar)14(y)-317.9(f)0(u)20.9(n)0(c)19.7(t)0(i)20.6(o)0(n)-313.2(i)0(s)-313.2(R)0(O)18.9(S)-317.7(ge)19.7(ne)19.7(ra)19.7(ti)14.8(on)20.8(,)-320.2(w)0(h)20(e)0(r)19.7(e)0(a)18.5(s)-323.4(ot)20.7(he)19.7(r)-317.8(e)0(n)13.9(z)0(y)19.7(m)0(e)18.4(s)]TJ
T*
[(pr)20.9(od)15.1(uc)19.7(e)-267.2(R)0(O)18.9(S)-271.6(as)-262.4(by)20.8(-p)20.9(ro)15.1(du)20.8(ct)19.5(s)-271.6(o)0(f)-261.4(e)0(n)19.7(z)0(y)19.7(m)0(a)18.4(t)0(i)20.6(c)-273(ac)18.5(ti)20.6(vi)20.7(ty)-261.5(\(2)20.9(1\))20.9(.)]TJ
1.0137 -1.1116 TD
[(Since)-255.5(the)-252.3(discovery)-259.8(of)-249.8(Nox2,)-256.4(six)-250.9(other)-254.4(Nox)-257.6(isoforms)-251.6(have)]TJ
-1.0137 -1.1174 TD
[(been)-248.6(identied,)-246.3(including)-247.6(Nox1,)-244.9(Nox3,)-250.6(Nox4,)-244.9(Nox5,)-244.9(Duox1,)]TJ
0 -1.1116 TD
[(and)-246.4(Duox2)-242.5(\(83,)-242.9(115\).)-244(The)-241.8(existence)-250.8(of)-244.1(multiple)-242.1(homologs)-246.1(of)]TJ
T*
[(Nox2)-224.1(in)-227(nonphagocytic)-231.2(cells/tissues)-230.8(suggests)-228.4(that)-224.7(production)]TJ
0 -1.1174 TD
[(of)-313.2(ROS)-321.8(in)-313.4(these)-318.8(sites)-317.6(is)-313.2(distinct)-321.3(and)-315.5(different)-317.7(from)-316.6(host)-315.4(de-)]TJ
0 -1.1116 TD
[(fense)-284.1(functions)-281.8(\(6\).)]TJ
1.0137 -1.1116 TD
[(Although)-430.4(there)-428.4(has)-430.5(been)-427.2(enormous)-431.4(advancement)-434(in)-428.5(the)]TJ
-1.0137 -1.1174 TD
[(eld)-264.7(of)-261.4(Nox)-263.4(biology,)-259.1(the)-263.8(specic)-264.4(biological)-267.3(signicance)-264.3(and)]TJ
0 -1.1116 TD
[(mechanisms)-316.2(of)-313.2(regulation)-319(of)-307.4(the)-315.6(different)-317.7(Noxs)-310.3(still)-316.8(remain)]TJ
T*
[(elusive)-263.5(\(6\).)-260.1(Rodent)-262.4(vascular,)-263.3(cardiac,)-269.3(and)-257.9(renal)-261.4(cells)-267.1(express)]TJ
0 -1.1174 TD
[(Nox1,)-244.9(Nox2,)-244.9(and)-246.4(Nox4,)-244.9(and)-246.4(in)-244.2(humans,)-248.4(Nox5)-247.2(is)-244(also)-247.4(present)]TJ
0 -1.1116 TD
[(\(64,)-427.2(85,)-420.3(107\).)-428.3(These)-429.3(Noxs)-425.5(have)-427.2(been)-421.4(implicated)-431(in)-422.8(many)]TJ
T*
[(redox-sensitive)-210(pathophysiological)-208.1(proces)-8.7(ses)-205.7(in)-203.9(the)-206.2(heart)-203.8(and)]TJ
T*
[(vascular)-496(and)-488.3(renal)-497.5(systems)-493.5(\(64,)-490.5(85,)-489.5(107\))-488.2(and)-494(have)-490.5(been)]TJ
0 -1.1174 TD
[(suggested)-288.4(to)-284.6(be)-285.6(a)-284.5(cause)-285.3(of)-284.4(altered)-287.9(redox)-288.9(status)-284.1(in)-284.6(cardiovas-)]TJ
0 -1.1116 TD
[(cular)-284.4(disease,)-285.1(including)-282.2(hypertension)-280.5(and)-280.9(atherosclerosis.)]TJ
/F3 1 Tf
8.9663 0 0 8.9663 62.022 127.7858 Tm
[(ROS)-332.6(and)-338.2(Hypertension)]TJ
/F5 1 Tf
9.843 0 0 9.843 72 111.3448 Tm
[(Mechanisms)-488.7(contributing)-481.4(to)-486.1(hypertension)-482.1(are)-489.4(complex,)]TJ
-1.0137 -1.1116 TD
[(involving)-528.7(many)-525.2(pathological)-535.6(processes,)-528.8(including)-529.8(altered)]TJ
T*
[(renal)-416.9(Na)]TJ
/F9 1 Tf
7.3823 0 0 6.5614 97.3417 93.8268 Tm
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 105.5055 89.4614 Tm
[(regulation,)-414.6(endothelial)-413.5(dysfunction,)-414.2(vascular)-415.4(re-)]TJ
-4.4177 -1.1174 TD
[(modeling,)-372(vascular)-380.8(hypercontractility,)-374.2(arterial)-375.5(calcication,)]TJ
0 -1.1116 TD
[(immune)-298.4(cell)-300.7(activation,)-294.9(and)-298.2(inammation)-299.4(\(106,)-295.8(114\).)-295.8(Com-)]TJ
T*
[(mon)-350.1(to)-347.9(these)-347.6(processes)-358.4(is)-347.7(oxidative)-346.7(stress)-352.9(due)-350(to)-347.9(excessive)]TJ
25.504 67.9242 TD
[(Nox-derived)-533.8(ROS)-529.2(generation,)-530.8(reduced)-529.5(nitric)-532.3(oxide)-530.9(\(NO\))]TJ
0 -1.1174 TD
[(bioavailability,)-611.9(and)-609.2(decreased)-608.8(antioxidant)-614(capacity)-607(\(31\).)]TJ
0 -1.1116 TD
[(Oxidative)-226.6(stress)-220.4(is)-221(associated)-228.6(with)-218.6(increased)-227.6(redox)-219.7(signaling,)]TJ
T*
[(activation)-614(of)-606.9(transcription)-610.2(factors,)-606.6(stimulation)-608.2(of)-606.9(proin-)]TJ
T*
[(ammatory)-279.6(and)-280.9(probrotic)-277.2(signaling)-276.2(pathways,)-280.3(induction)-276.4(of)]TJ
0 -1.1174 TD
[(stress-r)-9.4(elated)-206.2(kinases)-205.6(and)-200.3(DNA)-207.5(damage,)-204.8(molecular)-204.9(processes)]TJ
0 -1.1116 TD
[(that)-282.3(lead)-283.3(to)-278.8(cell)-283.5(damage,)-285.5(and)-280.9(vascular)-282.9(dysfunction)-284(\(49\).)]TJ
1.0137 -1.1116 TD
[(Ab)20(no)15.1(rm)19.6(al)-337.6(re)13.9(do)20.8(x)-352.4(s)0(i)20.9(g)0(n)20.8(a)0(l)19.5(i)0(n)20.7(g)-352.4(an)19.7(d)-352.4(o)0(x)20.8(i)0(d)20.7(a)0(t)13.8(i)0(v)20.7(e)-353.6(st)20.9(re)19.7(ss)-341.6(ha)19.7(ve)-343.2(be)19.7(en)]TJ
-1.0137 -1.1174 TD
[(sh)15.3(ow)20(n)-346.7(t)0(o)-342.2(p)0(l)20.7(a)0(y)-343.2(a)-347.8(ro)20.9(le)-343.3(in)-336.4(de)19.7(ve)13.9(lo)20.7(pm)19.6(en)19.7(t)-346.8(o)0(f)-342(h)0(y)20.8(p)0(e)19.7(r)0(t)20.7(e)0(n)13.9(s)0(i)20.9(o)0(n)-336.3(i)0(n)-342.2(e)0(x)19.7(-)]TJ
0 -1.1116 TD
[(pe)13.9(ri)20.7(me)18.4(nt)20.7(al)-274.2(mo)19.6(de)19.7(ls)15.1(.)-279.9(I)0(n)-278.6(a)0(n)19.7(g)0(i)20.7(o)0(t)20.7(e)0(n)19.7(s)0(i)15.1(n)-283.3(II)-272.8(\(A)20(ng)-272.9(II)15.1(\)-)20.9(in)20.7(du)20.8(ce)12.8(d)-283.3(h)0(y)20.8(p)0(e)19.7(r)0(-)]TJ
T*
[(te)13.8(ns)21(io)20.7(n)-225.7(i)0(n)-215.4(r)0(o)15.1(d)0(e)19.7(n)0(t)20.7(s)0(,)-217.4(p)0(r)20.9(o)0(d)20.8(u)0(c)19.7(t)0(i)14.8(o)0(n)-215.3(o)0(f)-215.3(O)]TJ
7.3823 0 0 6.5614 447.4771 613.9274 Tm
(2)Tj
/F9 1 Tf
.4838 .9159 TD
(-)Tj
/F5 1 Tf
9.843 0 0 9.843 457.3983 615.5715 Tm
[(an)19.7(d)-225.7(H)]TJ
7.3823 0 0 6.5614 480.6424 613.9274 Tm
(2)Tj
9.843 0 0 9.843 484.2141 615.5715 Tm
(O)Tj
7.3823 0 0 6.5614 491.244 613.9274 Tm
(2)Tj
9.843 0 0 9.843 497.14 615.5715 Tm
[(is)-215.2(in)15(cr)19.7(ea)18.5(se)19.9(d)-225.7(i)0(n)]TJ
-18.7018 -1.1174 TD
[(va)13.9(sc)19.9(ul)20.7(ar)19.7(,)-337.5(r)0(e)19.7(n)0(a)19.7(l)0(,)-327.2(c)0(a)18.5(r)0(d)20.9(i)0(a)19.5(c)0(,)-328.2(a)0(n)19.7(d)-335.2(ne)19.7(ur)20.9(al)-326(ce)18.5(ll)20.6(s)-335(a)0(n)19.7(d)-335.2(an)19.7(ti)14.8(ox)20.8(id)20.7(an)19.7(t)-335.3(e)0(n)19.7(-)]TJ
0 -1.1116 TD
[(zy)13.9(ma)18.4(ti)20.6(c)-417(a)0(c)18.5(t)0(i)20.6(v)0(i)14.9(t)0(y)-405.5(i)0(s)-411.1(r)0(e)19.7(d)0(u)20.8(c)0(e)18.5(d)-421.5(\(1)20.9(3,)-407.7(26)20.8(,)-418.1(7)0(1)20.8(,)-418.1(95)20.8(,)-418.1(9)0(6)20.8(\))0(.)-413.4(O)0(x)20(i)0(d)20.7(a)0(t)19.5(i)0(v)20.7(e)]TJ
T*
[(st)15.1(re)19.7(ss)-376.2(ha)19.7(s)-381(a)0(l)19.6(s)0(o)-376.4(b)0(e)19.7(e)0(n)-372(d)0(e)19.7(m)0(o)19.6(n)0(s)15.3(t)0(r)20.7(a)0(t)19.5(e)0(d)-372(i)0(n)-376.7(s)0(a)19.9(l)0(t)20.6(-)0(s)21.1(e)0(n)13.9(s)0(i)20.9(t)0(i)20.6(v)0(e)-372(f)0(o)15.1(r)0(m)19.6(s)-381(of)]TJ
T*
.0121 Tc
[(hyp)5.2(er)5.3(tensi)5.1(o)-.5(n)-438.2(\()5.3(29)5.2(\).)-434.8(Rats)-438.1(wit)5.1(h)-438.3(de)]TJ
13.6332 0 TD
.0123 Tc
[(ox)5.4(ycort)5.3(icos)5.6(ter)5.5(o)-.3(n)5.4(e)-439.2(acet)5.3(at)5.3(e)]TJ
-13.6332 -1.1174 TD
.0119 Tc
[(sal)4.9(t)-.8(-)5.1(i)-.8(nd)5(uced)-559.4(min)5(e)-1.9(r)5.1(a)-1.9(lo)5(co)5(rt)4.9(icoid)-559.4(h)5(yp)5(ert)4.9(e)-1.9(n)5(s)-.5(i)4.9(o)-.7(n)-559.4(e)-1.9(x)5(h)-.7(i)4.9(b)-.7(i)4.9(t)-565.3(ele-)]TJ
0 -1.1116 TD
.0134 Tc
[(vat)6.4(e)-.4(d)-200.8(v)6.5(as)6.7(cul)6.4(a)-.4(r)-200.8(O)]TJ
7.3823 0 0 6.5614 379.8991 548.1636 Tm
0 Tc
(2)Tj
/F9 1 Tf
.5145 .9159 TD
(-)Tj
/F5 1 Tf
9.843 0 0 9.843 389.9338 549.8077 Tm
.0069 Tc
[(pr)-5.7(od)-5.7(uc)-6.9(t)-5.8(i)-.1(o)-5.7(n)-207.3(du)-5.7(e)-208.5(t)-.1(o)-213.1(a)-1.1(c)-6.9(t)-.1(i)-5.8(v)0(a)-6.9(t)-.1(i)-5.8(o)-5.7(n)-207.3(o)0(f)-207.3(N)-6.6(ox)-5.7(s)-207.1(a)-6.9(nd)]TJ
-7.8102 -1.1116 TD
.0072 Tc
[(m)-6.6(i).2(t)-5.5(o)-5.4(ch)-5.4(on)-5.4(dr)-5.4(i)-5.5(a)-.8(l)-218.7(o)-5.4(xi)-5.5(da)-6.6(s)-5.2(e)-.8(s)-218.3(a)-6.6(n)-5.4(d)-218.5(un)-5.4(co)-5.4(up)-5.4(l)-5.5(i).2(n)-5.4(g)-218.5(of)-224.3(en)-5.4(do)-5.4(th)-5.4(el)-5.5(i)-5.5(a)-.8(l)-218.7(n)-5.4(it)-5.5(r)-5.4(i).2(c)]TJ
0 -1.1174 TD
.0124 Tc
[(oxi)5.4(de)-375.8(s)5.7(y)-.2(n)5.5(t)-.3(h)5.5(a)-1.4(se)-370(\(11)5.5(0,)-371.2(13)5.5(3\))5.6(.)-376.9(N)4.7(ox)5.5(1-d)5.5(ep)5.5(en)5.5(dent)-374.7(ROS)-374.4(p)5.5(ro)5.5(duc-)]TJ
0 -1.1116 TD
.0115 Tc
[(tio)4.6(n)-277.6(h)-1.1(as)-283.1(als)4.8(o)-277.6(been)-277.6(demons)4.8(tr)4.7(ated)-277.6(in)-277.6(exp)4.6(e)-2.3(ri)4.5(ment)4.5(al)-277.7(mod)4.6(e)-2.3(l)4.5(s)-283.1(o)4.6(f)]TJ
T*
.0121 Tc
[(pul)5.1(mo)5.2(nary)-426.7(h)5.2(y)-.5(p)5.2(e)-1.7(r)5.3(t)-.6(en)5.2(si)5.1(on)-426.7(\()5.3(56\))-420.9(an)5.2(d)-426.7(s)-.3(eems)-426.5(to)-426.7(b)5.2(e)-427.9(es)5.4(peciall)5.1(y)]TJ
0 -1.1174 TD
[(impor)5.3(tant)-340.5(i)5.1(n)-340.3(arteri)5.1(al)-340.5()5.4(b)-.5(r)5.3(o)-.5(si)5.1(s)-340.1(a)4.1(nd)-340.3(v)5.2(a)-1.7(s)5.4(c)-1.7(ul)5.1(ar)-334.5(ag)5.2(ing)-334.6(i)-.6(n)-340.3(s)5.4(tr)5.3(oke-)]TJ
0 -1.1116 TD
[(pro)5.3(ne)-278(sp)5.3(on)5.3(taneous)5.5(ly)-276.9(h)5.3(ypert)5.2(en)5.3(siv)5.3(e)-278(rats)-276.7(\(5)5.3(2\).)]TJ
1.0137 -1.1116 TD
-.0214 Tc
[(Wh)-5.2(ile)-340.4(ex)-5.2(ten)-5.2(s).7(i)-5.3(v).5(e)-334.7(e)-6.4(xpe)-6.4(ri)-5.3(ment)-5.4(al)-339.4(dat)-5.3(a)-334.7(s)-5(upp)-5.2(or)-5.2(t)-333.7(a)-340.4(cau)-5.2(sat)-5.4(i).4(v)-5.2(e)-334.7(ro)-5.2(le)]TJ
-1.0137 -1.1174 TD
-.0171 Tc
[(fo)4.8(r)-352.2(o)4.8(xi)4.7(d)4.8(a)-2.1(t)4.7(i)-1(v)4.8(e)-353.4(s)5(t)4.7(ress)-346.3(in)-346.5(hy)4.8(per)4.9(t)-1.1(en)4.8(si)4.7(o)4.8(n)-.9(,)-348.8(t)-1(h)4.8(e)3.7(re)-347.7(is)-346.3(a)-353.4(p)4.8(au)4.8(cit)4.7(y)-352.3(o)4.8(f)-352.2(evi)4.7(-)]TJ
0 -1.1116 TD
-.0216 Tc
[(d)-5.4(e)-.8(n)-5.4(c)-.8(e)-225.4(f).4(o)-5.4(r)-224.2(a)-225.4(d).3(i)-5.5(r).4(ec)-6.6(t)-224.4(r).4(ol)-5.5(e)-225.4(o).3(f)-224.3(R)-6.5(OS)-224.1(in)-230(the)-225.4(p)-5.4(ath)-5.4(oph)-5.4(ys)-5.2(iol)-5.6(ogy)-230(of)-224.2(hu)-5.4(man)]TJ
T*
-.0178 Tc
[(hy)4.1(per)4.2(t)-1.7(en)4.1(si)4(o)4.1(n)-185.9(\()4.2(8)-1.6(2)4.1(,)-182.5(84)4.1(,)-182.5(1)4.1(01)4.1(\))4.2(.)-188.3(Ho)4.1(wev)4.1(e)-2.8(r)4.2(,)-182.5(man)4.1(y)-180.2(cl)4(in)4.1(i)4(c)-2.8(al)-180.3(st)4(ud)4.1(i)4(e)-2.8(s)-180(h)-1.6(av)4.1(e)]TJ
T*
-.0216 Tc
[(d)-5.4(e)-.8(mo)-5.4(ns)-5.2(tra)-6.6(t).2(ed)-212.8(a)-213.9(p).3(o)-5.4(s).5(it)-5.5(iv)-5.4(e)-208.2(a)-6.6(ss)-5.2(oci)-5.6(a)-.8(ti)-5.5(on)-212.8(be)-6.6(twe)-6.6(e)-.8(n)-212.8(b).3(lo)-5.4(od)-212.8(pr)-5.4(ess)-5.2(u).4(r)-5.4(e)-213.9(and)]TJ
0 -1.1174 TD
-.0177 Tc
[(pl)4.1(as)4.4(ma)-561.4(l)4.1(e)3.1(vel)4.1(s)-560(of)-554.4(bi)4.1(o)4.2(m)-2.7(ar)4.3(ker)4.3(s)-560(o)4.2(f)-560.2(ox)4.2(i)4.1(d)-1.5(at)4.1(iv)4.2(e)-561.4(s)4.4(t)4.1(r)-1.5(ess)4.4(,)-556.8(in)4.2(clu)4.2(d)4.2(i)-1.6(n)4.2(g)]TJ
0 -1.1116 TD
-.0215 Tc
[(m)-6.5(a)-.7(lo)-5.3(ndi)-5.5(ald)-5.3(e)-.7(hy)-5.3(de)-6.5(,)-629.7(F).6(2)-5.3(-).5(i)-5.4(s).6(op)-5.3(ro)-5.3(sta)-6.5(n).4(es)-5.1(,)-629.7(a)-6.5(nd)-633.1(ad)-5.3(van)-5.3(ced)-633.1(o)-5.3(x).4(id)-5.3(ati)-5.4(o).4(n)]TJ
T*
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[(r)-5.6(o).1(l)-5.7(e)-173.8(of)-172.6(p)-5.6(22p)-5.6(hox)-5.6(-d)-5.6(epe)-6.8(nde)-6.8(nt)-172.8(No)-5.6(xs)-172.5(\()-5.6(N)-.7(o)-5.6(x1,)-175(No)-5.6(x2,)-175(a)-6.8(n).1(d)-172.6(N)-.7(o)-5.6(x).1(4)-5.6(\))-172.6(in)-172.6(t)-5.7(h).1(e)]TJ
0 -1.1116 TD
-.0216 Tc
[(v)-5.4(a)-.8(s)-5.2(c)-.8(ul)-5.5(ar)-166.7(sys)-5.2(t).2(e)-6.6(m)-162.2(an)-5.4(d)-166.7(d).3(is)-5.2(cus)-5.2(s)-166.5(in)-166.7(det)-5.5(a)-.8(i)-5.5(l)-161.1(t)-5.5(h).3(e)-167.9(i).2(mp)-5.4(ort)-5.5(a)-.8(nc)-6.6(e)-162.1(o)-5.4(f)-166.7(p22)-5.4(pho)-5.4(x-)]TJ
T*
[(d)-5.3(e)-.7(pe)-6.5(nde)-6.5(nt)-379.8(N)-6.2(oxs)-5.1(,)-382(s).6(p)-5.3(eci)-5.4(ca)-6.5(lly)-385.5(Nox)-5.3(5).4(,)-382(w)-.4(h)-5.3(i).3(ch)-385.5(is)-379.5(e)-6.5(m)-.8(er)-5.3(gin)-5.3(g)-379.7(as)-385.3(an)]TJ
0 -1.1174 TD
-.0214 Tc
[(i)-5.3(m)-.7(po)-5.2(rta)-6.4(n).5(t)-253(N)-.3(o)-5.2(x)-247.1(i)-5.3(s).7(o)-5.2(f).6(or)-5.2(m)-248.3(i)-5.3(n)-247.1(h)-5.2(uma)-6.4(n)-247.1(d)-5.2(i).4(s)-5(eas)-5(e.)]TJ
/F3 1 Tf
8.9663 0 0 8.9663 59.7543 577.1337 Tm
0 Tc
[(p22phox-Dependent)-338(Nox)-335.3(Isoforms)]TJ
0 -1.2267 TD
[(in)-338(the)-334.7(Vascular)-335.3(System)]TJ
/F5 1 Tf
9.843 0 0 9.843 69.7323 549.751 Tm
[(p22phox,)-241.5(a)-244.2(nonglycosylated)-244.8(membrane-associated)-250.2(protein)]TJ
-1.0137 -1.1174 TD
[(of)-249.8(molecular)-256.8(mass)-248.3(22)-169.2(kDa,)-250.7(associates)-251.5(with)-253.2(Nox)-246.1(in)-250(a)-249.9(1:1)-251.1(ratio)]TJ
0 -1.1116 TD
[(\(114\).)-371.7(p22phox)-376.3(expression)-370.2(increases)-377.1(in)-370.9(response)-373.6(to)-370.9(Ang)-372.8(II)]TJ
T*
[(and)-407.6(is)-399.6(upregulated)-407.5(in)-405.5(experimental)-411.1(diabetes)-404(and)-401.9(hyperten-)]TJ
0 -1.1174 TD
[(sion.)-243.9(Its)-245.1(major)-244.1(functions)-247.3(are)-247.5(to)-238.5(stabilize)-249.9(Nox)-240.3(proteins)-246.2(\(Nox1,)]TJ
0 -1.1116 TD
[(Nox2,)-290.9(Nox3,)-285.2(and)-286.7(Nox4\))-288.6(and)-292.4(to)-284.6(interact)-289.1(with)-287.8(cytosolic)-294.7(orga-)]TJ
T*
[(nizer)-249.8(subunits)-244.8(for)-245.1(Nox1,)-244.9(Nox2,)-244.9(and)-246.4(Nox3)-241.4(\(106\).)-245(While)-251.1(Noxs)]TJ
0 -1.1174 TD
[(14)-187.6(have)-185.3(an)-181.9(obligatory)-185.3(need)-191(for)-181.8(p22phox)-186.3(for)-181.8(activation,)-191.2(Nox5)]TJ
0 -1.1116 TD
[(does)-281.8(not)-279.9(require)-286.6(p22phox)-278.4(for)-279.7(activity)-288.1(\(5\).)]TJ
1.0137 -1.1116 TD
-.0215 Tc
[(Details)-431.3(about)-425.9(vascular)-431.5(Nox1,)-428.1(Nox2,)-428.1(and)-425.8(N)-.4(ox4)-431.5(have)-426.9(been)]TJ
-1.0137 -1.1174 TD
-.0218 Tc
[(extensiv)-5.6(ely)-224.5(r).2(eviewed)-224.5(\().2(8,)-221.1(40,)-221.1(68,)-221.1(70,)-221.1(90\))-224.5(and)-218.7(only)-224.5(a)-1(n)-218.7(overview)-225.4(i)0(s)]TJ
0 -1.1116 TD
[(given)-195.6(h).2(ere)-196.8(f)-5.5(or)-195.6(completenes)-5.3(s).4(.)-192.2(T)-.9(he)-196.8(message)-196.7(and)-195.6(p).2(rotein)-195.6(for)-201.3(N)5.1(o)-5.5(x1,)]TJ
T*
-.0216 Tc
[(Nox2,)-278.5(and)-276.1(N)-.5(ox4)-270.4(have)-277.3(been)-276.1(identied)-276.1(in)-270.4(arteries)-275.9(in)-276.1(rodents)-275.9(a)-.8(nd)]TJ
T*
[(humans.)-157.5(All)-155.3(N)-.5(oxs)-155(are)-150.6(e)-.8(xpres)-5.2(sed)-149.4(t).2(o)-155.2(v).3(arying)-155.2(degrees)-155(in)-155.2(endothelial)]TJ
0 -1.1174 TD
[(cells,)-192(v).4(ascular)-189.6(s).6(mooth)-189.6(m)5(uscle)-190.8(cells,)-192(p).4(erivascular)-189.6(a)-.7(dipocytes,)-186.2(a)-.7(nd)]TJ
0 -1.1116 TD
[(br)-5.5(oblasts)-218.4(\()-5.5(36,)-221(103,)-221(112\).)-226.7(N)-.6(ox4)-218.6(is)-224.2(abundant)-224.5(in)-224.4(endothelial)-218.8(cells)-5.3(.)]TJ
T*
[(Nox1)-258.9(and)-258.9(N)-.6(ox2)-253.2(are)-260.1(e)-.9(xpressed)-258.9(i).1(n)-253.2(v).2(as)-5.3(cul)-5.6(a)4.8(r)-258.9(s).4(mooth)-258.9(m)-1(uscle)-254.3(cells,)]TJ
0 -1.1174 TD
[(with)-189.7(Nox1)-189.7(being)-189.7(p).3(redominant)-189.9(i).2(n)-189.7(l).2(arge)-185.1(conduit)-189.9(a)-.8(rteries)-189.5(a)-.8(nd)-189.7(Nox2)]TJ
0 -1.1116 TD
[(in)-281.9(peripheral)-276.3(a)-.8(rteries)-281.7(\().4(68\).)-278.5(C)-.7(onstitutively)-276.1(active)-277.3(N)-.5(ox4)-281.9(seems)-275.9(t).2(o)]TJ
T*
-.0214 Tc
[(play)-252.9(a)-248.3(r).6(ole)-254(i).4(n)-247.1(b).5(asal)-253(generation)-247.1(o).5(f)-247.1(R)-.5(OS.)]TJ
1.0137 -1.1174 TD
0 Tc
[(Th)19.6(e)-238.4(f)0(u)20.9(n)0(c)19.7(t)0(i)20.6(o)0(n)-226.8(o)0(f)-226.8(N)0(o)20(x)0(-)20.9(d)0(e)19.7(r)0(i)15(v)0(e)19.7(d)-231.5(RO)18.9(S)-237.1(i)0(n)-227(t)0(h)20.7(e)-238.4(va)19.7(sc)19.9(ul)20.7(ar)-228(sy)21(st)20.9(em)-229.2(is)]TJ
-1.0137 -1.1116 TD
[(co)13.9(m)15(p)0(l)15(e)0(x)-181.9(a)0(n)13.9(d)-191.2(de)13.9(pe)19.7(nd)20.8(s)-196.7(o)0(n)-186.5(t)0(h)20.7(e)-198.1(ta)19.6(rg)20.9(et)-187.8(ce)18.5(ll)-186.8(ty)20.7(pe)19.7(,)-193.5(p)0(r)15.1(e)0(d)19.7(o)0(m)19.6(i)0(n)20.7(a)0(n)19.7(t)-197.1(No)20(x)]TJ
T*
[(is)15.1(of)20.9(or)20.9(m,)-253.4(ty)20.7(pe)-251(of)-255.6(sp)21(ec)18.5(ie)19.5(s)-265.8(g)0(e)19.7(n)0(e)19.7(r)0(a)19.7(t)0(e)19.6(d)0(,)-252.2(s)0(t)20.9(i)0(m)19.5(u)0(l)14.9(a)0(t)19.5(i)0(n)20.7(g)-260.3(fa)19.7(ct)19.5(or)15.1(,)-256.9(a)0(n)13.9(d)-260.3(re)19.7(-)]TJ
T*
[(do)15.1(x)-467.6(s)0(t)15.1(a)0(t)19.5(e)0(.)-460.7(A)0(n)14.2(g)-467.6(II)-468.7(an)19.7(d)-473.4(o)0(t)20.7(h)0(e)19.7(r)-473.4(pr)20.9(oh)20.8(yp)20.8(er)14(te)19.6(ns)21(iv)20.7(e)-474.6(f)0(a)19.7(c)0(t)19.5(o)0(r)15.1(s)-473.2(ca)18.5(us)21(e)]TJ
0 -1.1174 TD
[(up)15.1(re)19.7(gu)20.8(la)19.6(ti)20.6(on)-244.1(of)-244.1(va)19.7(sc)19.9(ul)20.7(ar)-245.2(No)20(x1)-244.1(an)19.7(d)-254.5(N)0(o)20(x)0(2)20.8(,)-251.1(im)13.7(po)20.8(rt)20.7(an)19.7(t)-254.7(i)0(n)-244.2(r)0(e)19.7(d)0(o)20.8(x)0(-)]TJ
0 -1.1116 TD
[(me)18.4(di)15(at)19.5(ed)-297.1(hy)15.1(pe)19.7(rt)20.7(en)19.7(si)20.9(on)-301.7(in)-301.8(va)19.7(ri)20.7(ou)15.1(s)-306.2(e)0(x)13.9(p)0(e)19.7(r)0(i)20.7(m)0(e)18.4(n)0(t)20.7(a)0(l)-303(m)0(o)19.6(d)0(e)19.7(l)0(s)20.9(.)-314.5(Va)18.8(s-)]TJ
T*
[(cu)13.9(la)19.5(r)-248.7(N)0(o)20(x)0(1)20.8(/)0(2)20.7(-)0(d)15.1(e)0(r)19.7(i)0(v)20.7(e)0(d)-239.5(R)0(O)18.9(S)-254.4(ha)19.7(s)-248.6(a)0(l)19.5(s)0(o)-243.9(b)0(e)19.7(e)0(n)-239.5(s)0(u)21(g)0(g)15.1(e)0(s)19.9(t)0(e)19.6(d)-248.8(in)-238.5(at)13.8(he)19.7(ro)20.9(-)]TJ
0 -1.1174 TD
[(sc)14.1(le)19.6(ro)20.9(si)20.9(s,)-534.2(di)20.7(ab)13.9(et)19.5(ic)-533.4(va)19.7(sc)19.9(ul)20.7(op)15.1(at)19.5(hy)20.8(,)-544.8(v)0(a)19.7(s)0(c)19.9(u)0(l)20.7(a)0(r)-533.2(r)0(e)14(m)0(o)19.6(d)0(e)19.7(l)0(i)20.6(n)0(g)20.8(,)-544.8(an)19.7(d)]TJ
0 -1.1116 TD
[(ao)13.9(rt)20.7(ic)-262.7(an)19.7(eu)19.7(ry)20.9(sm)-262.4(\(4)20.9(6,)-258(11)15.1(3,)-258(12)20.8(5,)-258(12)15.1(6\))20.9(.)-268.4(T)0(h)19.6(e)-273(ro)20.9(le)-262.7(of)-261.4(No)20(x4)-261.4(is)-261.3(le)19.6(ss)]TJ
T*
[(cl)13.8(ea)18.5(r)-277.5(b)0(e)19.7(c)0(a)18.5(u)0(s)21(e)-284.5(it)-267.4(ha)19.7(s)-283.1(b)0(e)19.7(e)0(n)-268.3(s)0(h)21(o)0(w)14.2(n)-277.6(to)-267.3(be)-274.1(bo)20.8(th)-267.3(va)19.7(so)15.3(in)20.7(ju)20.7(ri)20.7(ou)15.1(s)-277.4(a)0(n)19.7(d)]TJ
0 -1.1174 TD
[(va)13.9(so)21(pr)20.9(ot)20.7(ec)18.5(ti)14.8(ve)-222.2(\(8)20.9(,)-233.8(7)0(8)20.8(\))0(,)-223.4(d)0(e)19.7(p)0(e)19.7(n)0(d)20.8(i)0(n)20.7(g)-231.5(on)-226.8(ex)19.7(pe)19.7(ri)20.7(me)18.4(nt)20.7(al)-228.1(co)19.7(nd)20.8(it)20.6(io)20.7(ns)15.3(.)]TJ
0 -1.1116 TD
[(En)19.6(do)15.1(th)20.7(el)19.5(ia)19.5(l)-271.9(N)0(o)20(x)0(4)-261.4(i)0(n)20.7()0(u)21(e)0(n)13.9(c)0(e)18.5(s)-265.8(an)13.9(gi)20.7(og)20.8(en)19.7(es)19.9(is)-261.3(an)19.7(d)-271.8(v)0(a)19.7(s)0(c)14.1(u)0(l)20.7(a)0(r)-262.5(a)0(g)19.7(i)0(n)20.7(g)]TJ
T*
[(\(6)15.1(7\))20.9(,)-239.6(a)0(n)19.7(d)-237.2(pe)19.7(ri)15(va)19.7(sc)19.9(ul)20.7(ar)-233.7(No)20(x4)-226.8(is)-232.5(im)19.5(po)20.8(rt)20.7(an)13.9(t)-237.4(i)0(n)-232.7(v)0(a)19.7(s)0(c)19.9(u)0(l)20.7(a)0(r)-233.7(r)0(e)19.7(m)0(o)19.6(d)0(e)19.7(l)0(-)]TJ
0 -1.1174 TD
[(in)15(g)-398.5(i)0(n)-394(p)0(u)20.8(l)0(m)19.5(o)0(n)20.8(a)0(r)14(y)-398.5(hy)20.8(pe)13.9(rt)20.7(en)19.7(si)20.9(on)-393.9(\(4)20.9(\).)-396.2(In)-393.8(is)20.9(ch)19.7(em)18.5(ic)-395.1(or)-393.8(hy)20.8(po)20.8(xi)20.7(c)]TJ
0 -1.1116 TD
[(co)13.9(nd)20.8(it)20.6(io)20.7(ns)21(,)-153.2(e)0(n)19.7(d)0(o)20.8(t)0(h)15(e)0(l)19.5(i)0(a)19.5(l)-151(No)20(x4)-146.2(pl)20.7(ay)19.7(s)-150.7(a)-152(ro)15.1(le)-141.7(in)-140.6(bl)20.7(oo)15.1(d)20.8(br)20.9(ai)19.6(n)-150.8(b)0(a)13.9(r)0(r)20.9(i)0(e)19.6(r)]TJ
T*
[(br)15.1(ea)18.5(kd)20.8(ow)20(n)-346.7(a)0(n)19.7(d)-346.7(ne)19.7(ur)20.9(al)-337.6(au)19.7(to)20.7(to)20.7(xi)15(ci)19.5(ty)20.7(.)-343.3(N)0(o)20(x)0(4)]TJ
/F9 1 Tf
7.3823 0 0 6.5614 224.674 170.5323 Tm
(-)Tj
/F5 1 Tf
.5376 0 TD
(/)Tj
/F9 1 Tf
.2688 0 TD
(-)Tj
/F5 1 Tf
9.843 0 0 9.843 238.1102 166.1669 Tm
[(mi)19.5(ce)-338.6(we)18.8(re)-337.4(pr)20.9(o-)]TJ
-18.12 -1.1116 TD
[(te)13.8(ct)19.5(ed)-262.5(fr)20.9(om)-262.6(ox)20.8(id)20.7(at)13.8(iv)20.7(e)-273(s)0(t)20.9(r)0(e)19.7(s)0(s)15.5(,)-268.4(bl)20.7(oo)15.1(d)20.8(br)20.9(ai)19.5(n)-271.8(b)0(a)19.7(r)0(r)15.1(i)0(e)19.6(r)-271.8(le)19.6(ak)19.7(ag)19.7(e,)-264.9(an)19.7(d)]TJ
0 -1.1174 TD
[(ne)13.9(ur)20.9(on)20.8(al)-245.4(ap)19.7(op)20.8(to)15(si)20.9(s)-254.3(i)0(n)-244.2(a)-255.7(st)20.9(ro)15.1(ke)-245.3(mo)19.6(de)19.7(l)-254.7(\()0(1)20.9(2)0(\))20.9(,)-256.9(in)20.7(di)20.7(ca)18.5(ti)14.8(ng)-244.1(a)-255.7(p)0(a)19.7(t)0(h)20.7(o)0(-)]TJ
0 -1.1116 TD
[(lo)15(gi)20.7(ca)18.5(l)-283.5(r)0(o)20.9(l)0(e)-280(o)0(f)-272.9(N)0(o)20(x)0(4)-278.7(i)0(n)-273(t)0(h)15(i)0(s)-272.8(m)0(o)19.6(d)0(e)19.7(l)0(.)-275.4(N)0(o)20(x)0(4)-278.7(i)0(s)-272.8(a)0(l)19.5(s)0(o)-278.5(i)0(m)19.5(p)0(o)20.8(r)0(t)20.7(a)0(n)13.9(t)-283.5(in)]TJ
T*
[(b)15.2(ro)20.9(si)20.9(s)-242.8(a)0(n)19.7(d)-237.2(ca)18.5(rd)15.1(io)20.7(va)19.7(sc)19.9(ul)20.7(ar)-233.7(re)19.7(mo)19.6(de)19.7(li)14.8(ng)-226.8(\(6)20.9(3\))15.1(.)]TJ
1.0137 -1.1174 TD
-.0215 Tc
[(On)-281.8(t)-5.4(h).4(e)-282.9(o).4(th)-5.3(er)-281.7(ha)-6.5(nd,)-284.1(emer)-5.3(gi)-5.4(ng)-281.8(evi)-5.4(d).4(en)-5.3(ce)-282.9(in)-5.3(dic)-6.5(a)-.7(te)-6.5(s)-275.8(v)-5.3(as)-5.1(opr)-5.3(ote)-6.5(c)-.7(-)]TJ
-1.0137 -1.1116 TD
-.0195 Tc
[(tive)-378.9(and)-371.9(a)1.3(ntiatherosclerotic)-373.1(fu)]TJ
11.7901 0 TD
-.0214 Tc
[(nct)-5.3(i).4(o)-5.2(n).5(s)-373.6(f)-5.2(or)-379.6(end)-5.2(o).5(t)-5.3(h).5(el)-5.3(ial)-379.7(a)-.6(nd)-379.6(ca)-6.4(r-)]TJ
-11.7901 -1.1116 TD
-.0203 Tc
[(diom)-5.3(yoc)-5.3(yte)-183.8(N)-5(ox4)-182.7(because)-183.8(de)-5.3(letion)-176.9(of)-182.6(Nox4)-182.7(in)-182.7(these)-183.8(c)-5.3(ell)-182.8(t)-4.2(ype)-5.3(s)-182.5(i)1.5(s)]TJ
0 -1.1174 TD
-.0199 Tc
[(a)-4.9(s)2.2(sociate)-4.9(d)-476(with)-476(w)-4.6(o)2(rse)-477.2(c)-4.9(ardiovas)]TJ
13.0169 0 TD
-.0202 Tc
[(cular)-476.3(i)-4.1(njury)-482.1(a).6(nd)-482.1(endothelial)]TJ
-13.0169 -1.1116 TD
-.0215 Tc
[(d)-5.3(y).4(s)-5.1(f).5(un)-5.3(cti)-5.4(o).4(n)-299.1(i).3(n)-299.1(e)-6.5(xpe)-6.5(rim)-6.5(e)-.7(nt)-5.4(al)-299.2(mod)-5.3(e)-.7(l)-5.4(s)-298.9(of)-299(at)-5.4(her)-5.3(o).4(sc)-6.5(ler)-5.3(o).4(s)-5.1(i).3(s)-5.1(,)-295.6(ca)-6.5(rdi)-5.4(a)-.7(c)]TJ
T*
[(i)-5.5(s).5(c)-6.6(h).3(emi)-5.5(a)-.8(,)-284.2(a)-6.6(nd)-287.6(hyp)-5.4(er)-5.4(ten)-5.4(s).5(io)-5.4(n)-281.9(\()-5.4(86)-5.4(,)-284.2(1).3(3)-5.4(4).3(\).)-290(Rea)-6.6(s).5(on)-5.4(s)-287.4(f).4(or)-287.6(th)-5.4(e)-283(d)-5.4(is)-5.2(cre)-6.6(p).3(-)]TJ
25.5097 67.9242 TD
-.0199 Tc
[(ant)-286.1(r)-3.7(esults)-285.8(likely)-285.9(r)-3.7(ela)-4.9(t)1.9(e)-287.1(t)1.9(o)-285.9(t)1.9(he)-287.1(si)]TJ
12.1818 0 TD
-.0216 Tc
[(t)-5.6(e)-288.8(of)-287.6(No)-5.4(x4)-287.6(ac)-6.6(tiv)-5.4(ati)-5.5(on,)-290(ty)-5.4(pe)-288.8(and)]TJ
-12.1818 -1.1174 TD
[(si)-5.5(te)-283(of)-281.9(R)-6.4(O)-.5(S)-281.7(p).3(r)-5.4(odu)-5.4(cti)-5.5(on,)-284.2(an)-5.4(d)-281.9(e)-.8(xp)-5.4(eri)-5.5(m)-.9(en)-5.4(tal)-282(m)-.9(o)-5.4(d).3(e)-6.6(l).2(s)-281.7(s).5(t)-5.5(udi)-5.6(ed)-5.4(.)]TJ
1.0137 -1.1116 TD
0 Tc
[(T)15(h)0(e)-251(e)0(x)19.7(a)0(c)18.5(t)-254.7(ro)15.1(le)-245.4(of)-244.1(No)14.2(x4)-244.1(in)-244.2(hu)15.1(ma)18.4(ns)-243.9(is)-249.8(st)20.9(il)20.6(l)-254.7(u)0(n)15.1(c)0(l)19.5(e)0(a)18.5(r)0(,)-246.4(a)0(l)19.6(t)0(h)20.7(o)0(u)20.8(g)0(h)]TJ
-1.0137 -1.1116 TD
[(cl)19.5(in)20.7(ic)19.6(al)-274.2(st)20.9(ud)20.8(ie)19.6(s)-283.1(i)0(m)19.5(p)0(l)20.7(y)-283.3(th)20.7(at)-268.4(No)20(x4)-272.9(is)-272.8(im)19.5(po)20.8(rt)20.7(an)19.7(t)-283.5(i)0(n)-267.3()0(b)21(r)0(o)15.1(s)0(i)20.9(s)0(.)-269.3(V)0(a)18.8(r)0(-)]TJ
T*
[(io)20.7(us)-387.9(dr)20.9(ug)20.8(s)-398.3(a)0(n)19.7(d)-392.8(sm)19.8(al)13.8(l-)20.7(mo)19.6(le)19.6(cu)19.7(le)-389.4(in)20.7(hi)20.7(bi)20.7(to)15(rs)-382.1(ta)19.5(rg)15.1(et)19.5(in)20.7(g)-398.5(N)0(o)20(x)0(4)-382.3(i)0(n)]TJ
0 -1.1174 TD
[(pa)19.7(th)20.7(ol)20.7(og)20.8(ic)13.8(al)-274.2(b)21(ro)20.9(si)20.9(s)-283.1(a)0(r)19.7(e)-284.5(un)15.1(de)19.7(r)-283.3(d)0(e)19.7(v)0(e)19.7(l)0(o)20.7(p)0(m)19.6(e)0(n)19.7(t)-283.5(\(1)20.9(17)15.1(\).)-269.4(A)-284.2(N)0(o)20(x)0(1)20.8(/)0(4)]TJ
0 -1.1116 TD
[(in)20.7(hi)20.7(bi)20.7(to)15(r,)-177.3(GK)19.1(T1)19.6(36)20.8(90)20.8(1,)-177.3(is)-180.7(cu)19.7(rr)20.9(en)19.7(tl)14.8(y)-185.4(i)0(n)-175.1(P)0(h)15.2(a)0(s)19.9(e)-186.6(2)-185.4(c)0(l)13.8(i)0(n)20.7(i)0(c)19.6(a)0(l)-176.3(t)0(r)15(i)0(a)19.6(l)0(s)-174.9(f)0(o)20.9(r)]TJ
T*
[(tr)20.7(ea)18.5(ti)20.6(ng)-192.3(he)19.7(pa)19.7(ti)20.6(c)-203.8()0(b)21(r)0(o)20.9(s)0(i)20.9(s)-202.5(\(7)20.9(1\))20.9(.)-199.3(W)0(h)18.6(e)0(t)19.5(h)0(e)19.7(r)-202.7(su)21(ch)-193.4(ap)19.7(pr)20.9(oa)19.7(ch)19.7(es)-193.2(wi)19.8(ll)-186.8(be)]TJ
0 -1.1174 TD
[(be)19.7(ne)19.7(c)19.8(ia)19.6(l)-202.8(i)0(n)-186.6(c)0(a)18.5(r)0(d)20.9(i)0(o)20.7(v)0(a)19.7(s)0(c)14.1(u)0(l)20.7(a)0(r)-187.6()0(b)21(r)0(o)20.9(s)0(i)15.1(s)-196.7(an)19.7(d)-196.9(r)0(e)19.7(m)0(o)19.6(d)0(e)13.9(l)0(i)20.6(n)0(g)-186.5(i)0(s)-186.4(u)0(n)15.1(c)0(l)19.5(e)0(a)18.5(r)0(.)]TJ
/F3 1 Tf
8.9663 0 0 8.9663 310.8472 615.5148 Tm
[(p22phox-Independent)-337.4(Nox)-335.3(Isoforms:)-332.3(Focus)-335.6(on)-333.8(Nox5)]TJ
/F5 1 Tf
9.843 0 0 9.843 320.8251 599.0739 Tm
[(In)-365(addition)-373.2(to)-370.9(Noxs)-373.7(14,)-369.6(three)-370.8(other)-369.6(Nox)-372.8(isoforms)-372.6(have)]TJ
-1.0137 -1.1116 TD
[(been)-323.5(identied,)-326.9(including)-322.5(Nox5,)-325.5(Duox1,)-320.8(and)-327(Duox2,)-320.8(which)]TJ
T*
(share)Tj
/F11 1 Tf
2.4364 0 TD
(&)Tj
/F5 1 Tf
.9964 0 TD
[(50%)-321.1(homology)-321.2(with)-322.3(Nox2)-322.1(\(2,)-322.4(27\).)-317.7(These)-325.6(Noxs)-321.9(are)]TJ
-3.4328 -1.1116 TD
[(unique,)-207.2(in)-203.9(that)-207.4(they)-207.3(possess)-209.7(a)-209.6(long)-206.1(NH)]TJ
7.3823 0 0 6.5614 459.4393 564.6046 Tm
(2)Tj
9.843 0 0 9.843 465.1652 566.2487 Tm
[(terminus)-212.8(containing)-209.6(a)]TJ
-15.6779 -1.1174 TD
(Ca)Tj
7.3823 0 0 6.5614 321.7889 559.6156 Tm
(2)Tj
/F9 1 Tf
.5069 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 329.6125 555.2502 Tm
[(-binding)-199.1(EF-hand)-205.7(domain)-205(and)-206.1(do)-203.8(not)-205(require)-205.9(p22phox)-203.5(or)]TJ
-1.9065 -1.1116 TD
[(cytosolic)-311.9(Nox)-303.7(subuni)-6.6(ts)-307.4(for)-308.5(their)-306.4(activation.)-312.2(Nox5)-310.5(has)-309.5(a)-307.5(mo-)]TJ
T*
[(lecular)-310.9(mass)-311.7(of)]TJ
/F11 1 Tf
6.4969 0 TD
(&)Tj
/F5 1 Tf
1.0022 0 TD
[(85)-163.5(kDa)-310.6(and)-309.7(does)-310.6(not)-308.7(seem)-307.3(to)-307.6(be)-314.4(glycosy-)]TJ
-7.4991 -1.1174 TD
[(lated,)-264.9(whereas)-265.3(Duox1)-259.8(and)-263.6(Duox2)-265.6(have)]TJ
/F6 1 Tf
15.8392 0 TD
(N)Tj
/F5 1 Tf
.6681 0 TD
[(-glycosylation)-265.7(sites)]TJ
-16.5073 -1.1116 TD
[(and)-338.5(a)-342.1(molecular)-343.2(mass)-346.2(of)-336.2(160190)-169(kDa)-339.4(\(2\).)-340.7(These)-342.9(Noxs)-344.9(are)]TJ
T*
[(directly)-236.1(activated)-239.6(by)-238.3(Ca)]TJ
7.3823 0 0 6.5614 404.6172 504.8503 Tm
(2)Tj
/F9 1 Tf
.4992 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 412.3841 500.4849 Tm
[(,)-239.6(which)-232.3(binds)-235.8(to)-238.5(the)-235(EF-hand)-240.3(Ca)]TJ
7.3823 0 0 6.5614 538.866 504.8503 Tm
(2)Tj
/F9 1 Tf
.4992 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 546.6329 500.4849 Tm
(-)Tj
-23.9546 -1.1174 TD
[(binding)-382.4(domains,)-387.9(causing)-384.3(conformational)-389.1(change)-384.5(and)-384.6(acti-)]TJ
0 -1.1116 TD
[(vation)-278.7(of)-284.4(Nox)-280.6(to)-278.8(generate)-284.3(O)]TJ
7.3823 0 0 6.5614 422.7589 476.9007 Tm
(2)Tj
9.843 0 0 9.843 429.2219 478.5447 Tm
[(\(2,)-276.3(3,)-281(27\).)]TJ
/F12 1 Tf
8.9663 0 0 8.9663 310.8472 456.6046 Tm
(Duox1/2)Tj
/F5 1 Tf
9.843 0 0 9.843 320.8251 440.1636 Tm
[(Du)20(ox)20.8(1)-277.6(a)0(n)19.7(d)-277.6(Du)20(ox)15.1(2)-277.6(w)0(e)18.8(r)0(e)-268.3(o)0(r)20.9(i)0(g)14.9(i)0(n)20.7(a)0(l)19.5(l)0(y)-267.3(i)0(d)14.9(e)0(n)19.7(t)0(i)20.6()0(e)19.8(d)-277.6(in)-267.3(th)14.9(e)-278.7(t)0(h)20.7(y)0(r)20.9(o)0(i)20.7(d)]TJ
-1.0137 -1.1116 TD
[(gl)20.7(an)19.7(d)-225.7(a)0(n)19.7(d)-225.7(ar)19.7(e)-226.9(c)0(r)19.7(i)0(t)20.6(i)0(c)19.5(a)0(l)19.5(l)0(y)-215.4(i)0(n)20.7(v)0(o)15.1(l)0(v)20.7(e)0(d)-216.5(i)0(n)-209.7(r)0(e)14(d)0(o)20.8(x)0(-)20.9(d)0(e)19.7(p)0(e)19.7(n)0(d)15.1(e)0(n)19.7(t)-220.1(sy)15.3(nt)20.7(he)19.7(si)20.9(s)]TJ
T*
[(of)-238.3(th)20.7(yr)20.9(oi)14.9(d)-248.8(h)0(o)20.8(r)0(m)19.6(o)0(n)20.8(e)-249.9(\(1)20.9(0\))20.9(.)-251.1(D)0(u)20(o)0(x)20.8(1)0(/)14.9(2)-248.8(ar)19.7(e)-249.9(h)0(i)20.7(g)0(h)20.8(l)0(y)-238.5(e)0(x)19.7(p)0(r)15.1(e)0(s)19.9(s)0(e)19.9(d)-248.8(in)-238.5(th)14.9(e)]TJ
0 -1.1174 TD
[(th)20.7(yr)20.9(oi)20.7(d)-208.4(g)0(l)20.7(a)0(n)19.7(d)0(,)-200.4(b)0(u)20.8(t)-202.8(Du)14.2(ox)20.8(1)-202.7(h)0(a)13.9(s)-202.5(al)19.5(so)-197.8(be)19.7(en)-199.2(id)20.7(en)19.7(ti)14.8(e)19.8(d)-202.7(i)0(n)-198.2(l)0(o)20.7(w)-209.3(le)19.6(ve)19.7(ls)]TJ
0 -1.1116 TD
[(in)-273(re)14(sp)21(ir)20.7(at)19.5(or)15.1(y)-283.3(e)0(p)19.7(i)0(t)20.6(h)0(e)13.9(l)0(i)20.6(u)0(m)19.6(,)-285.7(wh)20(il)20.6(e)-290.2(D)0(u)20(o)0(x)20.8(2)-289.1(ha)19.7(s)-283.1(b)0(e)13.9(e)0(n)-274.1(i)0(d)20.7(e)0(n)19.7(t)0(i)14.8()0(e)19.8(d)-283.3(in)]TJ
T*
[(ga)19.7(st)20.9(ro)20.9(in)15(te)19.6(st)20.9(in)20.7(al)-274.2(gl)14.9(an)19.7(du)20.8(la)19.6(r)-283.3(e)0(p)19.7(i)0(t)14.8(h)0(e)19.7(l)0(i)20.6(u)0(m)19.6(,)-285.7(sa)19.9(li)20.6(va)19.7(ry)-278.6(gl)20.7(an)19.7(ds)21(,)-285.6(a)0(n)19.7(d)-283.3(tu)20.7(-)]TJ
0 -1.1174 TD
[(mo)19.6(rs)-232.4(\(3)20.9(2,)-234.9(12)20.8(8\))20.9(.)-245.3(L)0(i)19.5(t)0(t)20.6(l)0(e)-233.9(i)0(s)-232.5(k)0(n)15.1(o)0(w)20(n)-243(ab)19.7(ou)20.8(t)-243.1(D)0(u)20(o)0(x)20.8(s)-242.8(in)-232.7(th)15(e)-244.2(c)0(a)18.5(r)0(d)20.9(i)0(o)20.7(v)0(a)19.7(s)0(-)]TJ
0 -1.1116 TD
[(cu)19.7(la)19.6(r)-162.3(s)0(y)15.3(s)0(t)20.9(e)0(m)18.5(.)-164.7(A)-163.2(s)0(i)20.9(n)0(g)20.8(l)0(e)-153.2(s)0(t)15.1(u)0(d)20.8(y)-162.4(re)19.7(po)20.8(rt)15(ed)-153.1(th)20.7(at)-153.2(ao)19.7(rt)20.7(ic)-159(sm)19.8(oo)20.8(th)-152.1(mu)19.6(sc)19.9(le)]TJ
T*
[(ce)18.5(ll)20.6(s)-294.7(e)0(x)13.9(p)0(r)20.9(e)0(s)19.9(s)-294.6(lo)14.9(w)-295.7(l)0(e)19.6(v)0(e)19.7(l)0(s)-290.1(o)0(f)-284.4(D)0(u)20(o)0(x)20.8(1)-300.6(mR)18.6(NA)-286.2(\(5)20.9(9\))15.1(;)-295(h)0(o)20.8(w)0(e)18.8(v)0(e)19.7(r)0(,)-286.7(t)0(h)20.7(e)]TJ
0 -1.1174 TD
[(fu)20.9(nc)19.7(ti)20.6(on)-267.1(is)-261.3(un)20.8(cl)19.5(ea)12.8(r.)-263.7(In)-261.4(th)20.7(e)-273(h)0(e)19.7(a)0(r)14(t)0(,)-263.8(D)0(u)20(o)0(x)20.8(-)0(m)19.6(e)0(d)19.7(i)0(a)19.6(t)0(e)19.5(d)-277.6(H)]TJ
7.3823 0 0 6.5614 508.2518 339.8739 Tm
(2)Tj
9.843 0 0 9.843 511.8235 341.518 Tm
(O)Tj
7.3823 0 0 6.5614 518.7967 339.8739 Tm
(2)Tj
9.843 0 0 9.843 525.203 341.518 Tm
[(ge)19.7(ne)19.7(r-)]TJ
-21.7774 -1.1116 TD
[(at)19.5(io)20.7(n)-150.8(h)0(a)19.7(s)-150.7(be)19.7(en)-141.6(ob)20.8(se)14.1(rv)20.9(ed)-141.6(in)-140.6(ze)18.5(br)20.9(a)19.8(sh)-140.2(\(5)20.9(1\))15.1(,)-147.4(b)0(u)20.8(t)-151(to)-140.6(ou)20.8(r)-150.8(k)0(n)20.8(o)0(w)14.2(l)0(e)19.6(d)0(g)20.8(e)0(,)]TJ
T*
[(no)20.8(th)20.7(in)20.7(g)-243(i)0(s)-232.5(k)0(n)20.8(o)0(w)20(n)-237.2(ab)13.9(ou)20.8(t)-237.4(D)0(u)20(o)0(x)-232.6(i)0(n)-232.7(t)0(h)20.7(e)-238.4(ma)18.4(mm)18.4(al)19.5(ia)19.6(n)-243(h)0(e)19.7(a)0(r)19.7(t)0(.)]TJ
/F12 1 Tf
8.9663 0 0 8.9663 310.8472 297.6944 Tm
(Nox5)Tj
/F5 1 Tf
9.843 0 0 9.843 320.8251 281.2535 Tm
[(Nox5,)-216.1(of)-221(which)-220.8(there)-221(are)-224.5(multiple)-219.1(isoforms)-222.8(\(Nox5)]TJ
/F13 1 Tf
19.9286 0 TD
(a)Tj
/F5 1 Tf
.5011 0 TD
.2223 Tc
(,-)Tj
/F13 1 Tf
.8064 0 TD
0 Tc
(b)Tj
/F5 1 Tf
.5529 0 TD
.2165 Tc
(,-)Tj
/F13 1 Tf
.8006 0 TD
0 Tc
(c)Tj
/F5 1 Tf
.4377 0 TD
(,)Tj
-24.041 -1.1116 TD
[(and)-292.4(-)]TJ
/F13 1 Tf
2.0735 0 TD
(e)Tj
/F5 1 Tf
.6796 0 TD
[([also)-300.3(called)-298.3(Nox5S]\),)-294(is)-295.9(the)-298.3(most)-293.6(recently)-300.5(discovered)]TJ
-2.7531 -1.1174 TD
[(Nox)-177(and)-183(is)-180.7(unique)-180.7(\(Fig.)-180.6(1\))-180.7(\(20\).)-186.3(Nox5)]TJ
/F13 1 Tf
14.7103 0 TD
(e)Tj
/F5 1 Tf
.5645 0 TD
[(is)-180.7(a)-180.8(short)-184(form)-178.4(of)-180.7(Nox5)]TJ
-15.2747 -1.1116 TD
[(and)-292.4(lacks)-301.5(Ca)]TJ
7.3823 0 0 6.5614 362.1542 252.7369 Tm
(2)Tj
/F9 1 Tf
.4992 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 369.9211 248.3716 Tm
[(-binding)-297(domains.)-295.7(Unlike)-296.9(other)-300.5(isoforms,)-295.4(the)]TJ
-6.0016 -1.1116 TD
[(Nox5)-425.7(gene)-433(is)-428.3(absent)-429.3(in)-428.5(rodents,)-432.7(it)-428.7(generates)-429.2(ROS)-431.3(from)-431.8(a)]TJ
0 -1.1174 TD
[(single)-209.4(gene)-214.1(product,)-214(and)-211.8(does)-212.7(not)-210.8(require)-217.4(Nox)-211.5(subunits)-210.3(for)-216.3(its)]TJ
0 -1.1116 TD
[(activation.)-214.3(Its)-210.6(long,)-215.3(intracellular)-215.4(N-terminal)-217.4(domain)-210.7(with)-212.9(EF-)]TJ
T*
[(hands)-208.1(undergoes)-213.6(conformational)-216.3(changes)-212.6(upon)-211.8(Ca)]TJ
7.3823 0 0 6.5614 507.4581 208.9133 Tm
(2)Tj
/F9 1 Tf
.5069 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 517.3227 204.548 Tm
(binding.)Tj
-20.9768 -1.1174 TD
[(Increased)-492.4(cytoplasmic)-495.1(Ca)]TJ
7.3823 0 0 6.5614 417.033 197.9716 Tm
(2)Tj
/F9 1 Tf
.5069 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 429.6755 193.5496 Tm
[(concentration)-491.6(\([Ca)]TJ
7.3823 0 0 6.5614 505.814 197.9716 Tm
(2)Tj
/F9 1 Tf
.5069 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 513.6377 193.5496 Tm
(])Tj
7.3823 0 0 6.5614 516.9258 191.9622 Tm
(i)Tj
9.843 0 0 9.843 518.9668 193.5496 Tm
[(\))-490.6(i)0(s)-491.7(es-)]TJ
-21.1439 -1.1116 TD
[(sential)-188.8(for)-187.5(Nox5)-189.6(activation,)-191.2(as)-187.5(evidenced)-193.2(in)-186.6(cell)-191.3(studies)-187.3(where)]TJ
T*
[(ROS)-264.2(are)-270.5(not)-268.4(generated)-268.1(in)-267.3(Ca)]TJ
7.3823 0 0 6.5614 424.8566 176.0314 Tm
(2)Tj
/F9 1 Tf
.4992 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 432.6235 171.6661 Tm
[(-free)-266.9(buffer)-266.9(\(20,)-271.6(71\).)-265.9(Because)]TJ
-12.3718 -1.1116 TD
[(of)-365(its)-366.2(close)-370.6(association)-372.7(with)-368.4(Ca)]TJ
7.3823 0 0 6.5614 439.0865 165.0897 Tm
(2)Tj
/F9 1 Tf
.4992 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 446.8535 160.7244 Tm
[(,)-366.3(Nox5)-368.1(is)-370.8(likely)-365.3(to)-370.9(be)-366.2(in-)]TJ
-13.8175 -1.1174 TD
[(volved)-370.8(in)-376.7(Ca)]TJ
7.3823 0 0 6.5614 363.6849 154.0913 Tm
(2)Tj
/F9 1 Tf
.4992 0 TD
(+)Tj
/F5 1 Tf
9.843 0 0 9.843 371.4518 149.726 Tm
[(-activated)-378.9(redox-dependent)-378.4(processes.)-379.1(Nox5)]TJ
-6.1571 -1.1116 TD
[(regulation)-365(also)-362.6(depends)-366.9(on)-365.1(its)-360.5(gene)-363.8(expression,)-367.8(subcellular)]TJ
T*
[(localization,)-327.2(and)-321.2(post-translational)-323.2(modi)-6.7(cations.)-318.8(Of)-325.6(all)-321.5(the)]TJ
0 -1.1174 TD
[(Nox)-223(isoforms,)-226.3(only)-229.2(Nox5)-224.1(has)-228.9(recently)-225.6(been)-231.4(crystallized)-225.5(\(72\).)]TJ
/F3 1 Tf
8.9663 0 0 8.9663 310.8472 94.9039 Tm
[(Nox5)-333.4(Compartmentalization)-338.2(and)-331.9(Regulation)]TJ
/F5 1 Tf
9.843 0 0 9.843 320.8251 78.463 Tm
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