Molecular Mechanisms of Endothelial Dysfunction in Coronary Microcirculation Dysfunction

Overview

Journal J Thromb Thrombolysis

Specialty Cardiology & Vascular Diseases

Date 2023 Jul 19

PMID 37466848

Authors

Zhiyu Zhang

Xiangjun Li

Jiahuan He

Shipeng Wang

Jingyue Wang

Junqian Liu

Yushi Wang

Affiliations

Soon will be listed here.

Abstract

Coronary microvascular endothelial cells (CMECs) react to changes in coronary blood flow and myocardial metabolites and regulate coronary blood flow by balancing vasoconstrictors-such as endothelin-1-and the vessel dilators prostaglandin, nitric oxide, and endothelium-dependent hyperpolarizing factor. Coronary microvascular endothelial cell dysfunction is caused by several cardiovascular risk factors and chronic rheumatic diseases that impact CMEC blood flow regulation, resulting in coronary microcirculation dysfunction (CMD). The mechanisms of CMEC dysfunction are not fully understood. However, the following could be important mechanisms: the overexpression and activation of nicotinamide adenine dinucleotide phosphate oxidase (Nox), and mineralocorticoid receptors; the involvement of reactive oxygen species (ROS) caused by a decreased expression of sirtuins (SIRT3/SIRT1); forkhead box O3; and a decreased SK/IK expression in the endothelium-dependent hyperpolarizing factor electrical signal pathway. In addition, p66Shc is an adapter protein that promotes oxidative stress; although there are no studies on its involvement with cardiac microvessels, it is possible it plays an important role in CMD.

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References

Bradley C, Berry C . Definition and epidemiology of coronary microvascular disease. J Nucl Cardiol. 2022; 29(4):1763-1775. PMC: 9345825. DOI: 10.1007/s12350-022-02974-x. View

Ong P, Camici P, Beltrame J, Crea F, Shimokawa H, Sechtem U . International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2017; 250:16-20. DOI: 10.1016/j.ijcard.2017.08.068. View

Taqueti V, Di Carli M . Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018; 72(21):2625-2641. PMC: 6296779. DOI: 10.1016/j.jacc.2018.09.042. View

Vancheri F, Longo G, Vancheri S, Henein M . Coronary Microvascular Dysfunction. J Clin Med. 2020; 9(9). PMC: 7563453. DOI: 10.3390/jcm9092880. View

Duncker D, Bache R, Merkus D . Regulation of coronary resistance vessel tone in response to exercise. J Mol Cell Cardiol. 2011; 52(4):802-13. DOI: 10.1016/j.yjmcc.2011.10.007. View

Namani R, Lanir Y, Lee L, Kassab G . Overview of mathematical modeling of myocardial blood flow regulation. Am J Physiol Heart Circ Physiol. 2020; 318(4):H966-H975. PMC: 7191499. DOI: 10.1152/ajpheart.00563.2019. View

Karch R, Neumann F, Podesser B, Neumann M, Szawlowski P, Schreiner W . Fractal properties of perfusion heterogeneity in optimized arterial trees: a model study. J Gen Physiol. 2003; 122(3):307-21. PMC: 2234485. DOI: 10.1085/jgp.200208747. View

Chen C, Wei J, AlBadri A, Zarrini P, Merz C . Coronary Microvascular Dysfunction　- Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy. Circ J. 2016; 81(1):3-11. PMC: 8607842. DOI: 10.1253/circj.CJ-16-1002. View

Johnson N, Gould K, De Bruyne B . Autoregulation of Coronary Blood Supply in Response to Demand: JACC Review Topic of the Week. J Am Coll Cardiol. 2021; 77(18):2335-2345. DOI: 10.1016/j.jacc.2021.03.293. View

10.

Rogers P, Dick G, Knudson J, Focardi M, Bratz I, Swafford Jr A . H2O2-induced redox-sensitive coronary vasodilation is mediated by 4-aminopyridine-sensitive K+ channels. Am J Physiol Heart Circ Physiol. 2006; 291(5):H2473-82. DOI: 10.1152/ajpheart.00172.2006. View

11.

Otake A, Saitoh S, Takeishi Y . Hydrogen peroxide generated from cardiac myocytes impacts metabolic dilation in coronary arterioles. Int Heart J. 2010; 51(2):125-8. DOI: 10.1536/ihj.51.125. View

12.

Fukao M, Mason H, Britton F, Kenyon J, Horowitz B, Keef K . Cyclic GMP-dependent protein kinase activates cloned BKCa channels expressed in mammalian cells by direct phosphorylation at serine 1072. J Biol Chem. 1999; 274(16):10927-35. DOI: 10.1074/jbc.274.16.10927. View

13.

Nava E, Llorens S . The Local Regulation of Vascular Function: From an Inside-Outside to an Outside-Inside Model. Front Physiol. 2019; 10:729. PMC: 6581701. DOI: 10.3389/fphys.2019.00729. View

14.

Arrebola-Moreno A, Laclaustra M, Kaski J . Noninvasive assessment of endothelial function in clinical practice. Rev Esp Cardiol (Engl Ed). 2011; 65(1):80-90. DOI: 10.1016/j.recesp.2011.09.012. View

15.

Thijssen D, Bruno R, van Mil A, Holder S, Faita F, Greyling A . Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019; 40(30):2534-2547. DOI: 10.1093/eurheartj/ehz350. View

16.

Shimokawa H . 2014 Williams Harvey Lecture: importance of coronary vasomotion abnormalities-from bench to bedside. Eur Heart J. 2014; 35(45):3180-93. DOI: 10.1093/eurheartj/ehu427. View

17.

Shimokawa H, Godo S . Nitric oxide and endothelium-dependent hyperpolarization mediated by hydrogen peroxide in health and disease. Basic Clin Pharmacol Toxicol. 2019; 127(2):92-101. DOI: 10.1111/bcpt.13377. View

18.

Matoba T, Shimokawa H, Morikawa K, Kubota H, Kunihiro I, Urakami-Harasawa L . Electron spin resonance detection of hydrogen peroxide as an endothelium-derived hyperpolarizing factor in porcine coronary microvessels. Arterioscler Thromb Vasc Biol. 2003; 23(7):1224-30. DOI: 10.1161/01.ATV.0000078601.79536.6C. View

19.

Si H, Heyken W, Wolfle S, Tysiac M, Schubert R, Grgic I . Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel. Circ Res. 2006; 99(5):537-44. DOI: 10.1161/01.RES.0000238377.08219.0c. View

20.

Brahler S, Kaistha A, Schmidt V, Wolfle S, Busch C, Kaistha B . Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation. 2009; 119(17):2323-32. DOI: 10.1161/CIRCULATIONAHA.108.846634. View