Vascular Biology of Superoxide-Generating NADPH Oxidase 5-Implications in Hypertension and Cardiovascular Disease

被引:72
作者
Touyz, Rhian M. [1 ]
Anagnostopoulou, Aikaterini [1 ]
Camargo, Livia L. [1 ]
Rios, Francisco J. [1 ]
Montezano, Augusto C. [1 ]
机构
[1] Univ Glasgow, Inst Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland
关键词
Nox isoforms; vascular smooth muscle; endothelium; reactive oxygen species; oxidative stress; atherosclerosis; ANGIOTENSIN-II; OXIDATIVE STRESS; NITRIC-OXIDE; SMOOTH-MUSCLE; ENDOTHELIAL DYSFUNCTION; NAD(P)H OXIDASE; NOX FAMILY; HYDROGEN-PEROXIDE; BLOOD-PRESSURE; EXPRESSION;
D O I
10.1089/ars.2018.7583
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Significance: NADPH oxidases (Noxs), of which there are seven isoforms (Nox1-5, Duox1/Duox2), are professional oxidases functioning as reactive oxygen species (ROS)-generating enzymes. ROS are signaling molecules important in physiological processes. Increased ROS production and altered redox signaling in the vascular system have been implicated in the pathophysiology of cardiovascular diseases, including hypertension, and have been attributed, in part, to increased Nox activity. Recent Advances: Nox1, Nox2, Nox4, and Nox5 are expressed and functionally active in human vascular cells. While Nox1, Nox2, and Nox4 have been well characterized in models of cardiovascular disease, little is known about Nox5. This may relate to the lack of experimental models because rodents lack NOX5. However, recent studies have advanced the field by (i) elucidating mechanisms of Nox5 regulation, (ii) identifying Nox5 variants, (iii) characterizing Nox5 expression, and (iv) discovering the Nox5 crystal structure. Moreover, studies in human Nox5-expressing mice have highlighted a putative role for Nox5 in cardiovascular disease. Critical Issues: Although growing evidence indicates a role for Nox-derived ROS in cardiovascular (patho)physiology, the exact function of each isoform remains unclear. This is especially true for Nox5. Future Directions: Future directions should focus on clinically relevant studies to discover the functional significance of Noxs, and Nox5 in particular, in human health and disease. Two important recent studies will impact future directions. First, Nox5 is the first Nox to be crystallized. Second, a genome-wide association study identified Nox5 as a novel blood pressure-associated gene. These discoveries, together with advancements in Nox5 biology and biochemistry, will facilitate discovery of drugs that selectively target Noxs to interfere in uncontrolled ROS generation.
引用
收藏
页码:1027 / 1040
页数:14
相关论文
共 134 条
  • [11] Superoxide Dismutase 1 Limits Renal Microvascular Remodeling and Attenuates Arteriole and Blood Pressure Responses to Angiotensin II via Modulation of Nitric Oxide Bioavailability
    Carlstrom, Mattias
    Lai, En Yin
    Ma, Zufu
    Steege, Andreas
    Patzak, Andreas
    Eriksson, Ulf J.
    Lundberg, Jon O.
    Wilcox, Christopher S.
    Persson, A. Erik G.
    [J]. HYPERTENSION, 2010, 56 (05) : 907 - U373
  • [12] NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage
    Casas, Ana I.
    Geuss, Eva
    Kleikers, Pamela W. M.
    Mencl, Stine
    Herrmann, Alexander M.
    Buendia, Izaskun
    Egea, Javier
    Meuth, Sven G.
    Lopez, Manuela G.
    Kleinschnitz, Christoph
    Schmidt, Harald H. H. W.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (46) : 12315 - 12320
  • [13] Increased mitochondrial superoxide in the brain, but not periphery, sensitizes mice to angiotensin II-mediated hypertension
    Case, Adam J.
    Tian, Jun
    Zimmerman, Matthew C.
    [J]. REDOX BIOLOGY, 2017, 11 : 82 - 90
  • [14] IDENTIFICATION OF THE DEFECTIVE NADPH-OXIDASE COMPONENT IN CHRONIC GRANULOMATOUS-DISEASE - A STUDY OF 57 EUROPEAN FAMILIES
    CASIMIR, C
    CHETTY, M
    BOHLER, MC
    GARCIA, R
    FISCHER, A
    GRISCELLI, C
    JOHNSON, B
    SEGAL, AW
    [J]. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1992, 22 (06) : 403 - 406
  • [15] Angiotensin II, NADPH Oxidase, and Redox Signaling in the Vasculature
    Cat, Aurelie Nguyen Dinh
    Montezano, Augusto C.
    Burger, Dylan
    Touyz, Rhian M.
    [J]. ANTIOXIDANTS & REDOX SIGNALING, 2013, 19 (10) : 1110 - 1120
  • [16] Tetrahydrobiopterin reverse left ventricular hypertrophy and diastolic dysfunction through the PI3K/p-Akt pathway in spontaneously hypertensive rats
    Chang, Peng
    Wang, Qiongying
    Xu, Han
    Yang, Mina
    Lin, Xin
    Li, Xiuli
    Zhang, Zhengyi
    Zhang, Xiaowei
    Zhao, Feng
    Zhao, Xu
    Bai, Feng
    Yu, Jing
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2015, 463 (04) : 1012 - 1020
  • [17] Cloning, Characteristics, and Functional Analysis of Rabbit NADPH Oxidase 5
    Chen, Feng
    Yin, Caiyong
    Dimitropoulou, Christiana
    Fulton, David J. R.
    [J]. FRONTIERS IN PHYSIOLOGY, 2016, 7
  • [18] Nox5 stability and superoxide production is regulated by C-terminal binding of Hsp90 and CO-chaperones
    Chen, Feng
    Haigh, Steven
    Yu, Yanfang
    Benson, Tyler
    Wang, Yusi
    Li, Xueyi
    Dou, Huijuan
    Bagi, Zsolt
    Verin, Alexander D.
    Stepp, David W.
    Csanyi, Gabor
    Chadli, Ahmed
    Weintraub, Neal L.
    Smith, Susan M. E.
    Fulton, David J. R.
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2015, 89 : 793 - 805
  • [19] Enzymatic Regulation and Functional Relevance of NOX5
    Chen, Feng
    Wang, Yusi
    Barman, Scott
    Fulton, David J. R.
    [J]. CURRENT PHARMACEUTICAL DESIGN, 2015, 21 (41) : 5999 - 6008
  • [20] Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR
    Chen, X
    Touyz, RM
    Park, JB
    Schiffrin, EL
    [J]. HYPERTENSION, 2001, 38 (03) : 606 - 611