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Review
. 2021 Jul 31;10(8):1947.
doi: 10.3390/cells10081947.

Human Vascular Smooth Muscle Function and Oxidative Stress Induced by NADPH Oxidase with the Clinical Implications

Kazumi Takaishi  1 , Hiroyuki Kinoshita  2   3 , Shingo Kawashima  3 , Shinji Kawahito  1
Affiliations
Review

Human Vascular Smooth Muscle Function and Oxidative Stress Induced by NADPH Oxidase with the Clinical Implications

Kazumi Takaishi et al. Cells. .

Abstract

Among reactive oxygen species, superoxide mediates the critical vascular redox signaling, resulting in the regulation of the human cardiovascular system. The reduced form of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) is the source of superoxide and relates to the crucial intracellular pathology and physiology of vascular smooth muscle cells, including contraction, proliferation, apoptosis, and inflammatory response. Human vascular smooth muscle cells express NOX1, 2, 4, and 5 in physiological and pathological conditions, and those enzymes play roles in most cardiovascular disorders caused by hypertension, diabetes, inflammation, and arteriosclerosis. Various physiologically active substances, including angiotensin II, stimulate NOX via the cytosolic subunits' translocation toward the vascular smooth muscle cell membrane. As we have shown, some pathological stimuli such as high glucose augment the enzymatic activity mediated by the phosphatidylinositol 3-kinase-Akt pathway, resulting in the membrane translocation of cytosolic subunits of NOXs. This review highlights and details the roles of human vascular smooth muscle NOXs in the pathophysiology and clinical aspects. The regulation of the enzyme expressed in the vascular smooth muscle cells may lead to the prevention and treatment of human cardiovascular diseases.

Keywords: NADPH oxidase; human vascular smooth muscle; oxidase stress.

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Conflict of interest statement

Hiroyuki Kinoshita is a consult of IMI Co. Ltd., Koshigaya, Saitama, Japan. The funder had no role in the writing of the manuscript.

Figures

Figure 1
Figure 1
Superoxide and the reactive oxygen species derived from it in human vascular pathology are shown. Superoxide is a critical precursor of reactive oxygen species, including hydrogen peroxide, hydroxyl radical, and peroxynitrite. Superoxide dismutase metabolizes superoxide to hydrogen peroxide, whereas catalase inactivates hydrogen peroxide.
Figure 2
Figure 2
NOX 1, 2, 4, and 5 are expressed in human vascular smooth muscle cells. NOX1, 2, and 4 have the transmembrane subunit p22phox both in the active and inactive forms. NOX1 interacts with the cytosolic subunits NOXO1 or p47phox, NOXA1 or p67phox, and rac1 upon activation. NOX2 activates when it is associated with p47phox, p67phox, p40phox, and rac1. NOX4 is constitutively activated with the cytosolic p22phox subunit. NOX5 needs Ca2+ binding in the cytosol for activation.
Figure 3
Figure 3
Substances or agents acting on NOXs to reduce the function are shown. Isoflurane, albumin, nitric oxide donor, and prostacyclin possibly inactivate the NOX1 and 2, resulting in decreased oxidative stress in the human vascular smooth muscle cells. In addition, peroxisome proliferator-activated receptor (PPAR)-γ agonists may reduce human vascular oxidative stress since PPAR-γ regulates the NOX4-hydrogen peroxide signaling axis.
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References

    1. Zima A.V., Blatter L.A. Redox regulation of cardiac calcium channels and transporters. Cardiovasc. Res. 2006;71:310–321. doi: 10.1016/j.cardiores.2006.02.019. - DOI - PubMed
    1. Touyz R.M., Alves-Lopes R., Rios F.J., Camargo L.L., Anagnostopoulou A., Arner A., Montezano A.C. Vascular smooth muscle contraction in hypertension. Cardiovasc. Res. 2018;114:529–539. doi: 10.1093/cvr/cvy023. - DOI - PMC - PubMed
    1. Porter K.E., Riches K. The vascular smooth muscle cell: A therapeutic target in Type 2 diabetes? Clin. Sci. 2013;125:167–182. doi: 10.1042/CS20120413. - DOI - PubMed
    1. Kinoshita H. Effect of oxidative stress on vascular function, and the role of anesthetic. J. Anesth. 2012;26:141–142. doi: 10.1007/s00540-011-1283-4. - DOI - PubMed
    1. Guzik T.J., Chen W., Gongora M.C., Guzik B., Lob H.E., Mangalat D., Hoch N., Dikalov S., Rudzinski P., Kapelak B., et al. Calcium-dependent NOX5 nicotinamide adenine dinucleotide phosphate oxidase contributes to vascular oxidative stress in human coronary artery disease. J. Am. Coll. Cardiol. 2008;52:1803–1809. doi: 10.1016/j.jacc.2008.07.063. - DOI - PMC - PubMed

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