ACE2, a multifunctional protein – from cardiovascular regulation to COVID-19

Bäder, Michael; Turner, Anthony J.; Alenina, Natalia

doi:10.1042/cs20201493

Cited by 8 publications

(7 citation statements)

References 29 publications

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“…This transmembrane glycoprotein is widely expressed in the respiratory system but has also been detected in cardiomyocytes, endothelial cells, vascular smooth muscle cells and cardiac fibroblasts [ 36 ]. ACE2 is a monocarboxypeptidase whose catalytic site promotes the conversion of angiotensin II (Ang II), a prohypertensive and profibrotic peptide, into angiotensin (1-7) (Ang (1-7)), a vasodilatory and cardioprotective agent [ 37 ]. It, therefore, plays a pivotal role in the regulation of the RAAS [ 38 ].…”

Section: Ace2 Biology and Physiological Functionsmentioning

confidence: 99%

COVID-19-Induced Myocarditis: Pathophysiological Roles of ACE2 and Toll-like Receptors

Pannucci

Jefferson

Hampshire

et al. 2023

IJMS

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The clinical manifestations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection responsible for coronavirus disease 2019 (COVID-19) commonly include dyspnoea and fatigue, and they primarily involve the lungs. However, extra-pulmonary organ dysfunctions, particularly affecting the cardiovascular system, have also been observed following COVID-19 infection. In this context, several cardiac complications have been reported, including hypertension, thromboembolism, arrythmia and heart failure, with myocardial injury and myocarditis being the most frequent. These secondary myocardial inflammatory responses appear to be associated with a poorer disease course and increased mortality in patients with severe COVID-19. In addition, numerous episodes of myocarditis have been reported as a complication of COVID-19 mRNA vaccinations, especially in young adult males. Changes in the cell surface expression of angiotensin-converting enzyme 2 (ACE2) and direct injury to cardiomyocytes resulting from exaggerated immune responses to COVID-19 are just some of the mechanisms that may explain the pathogenesis of COVID-19-induced myocarditis. Here, we review the pathophysiological mechanisms underlying myocarditis associated with COVID-19 infection, with a particular focus on the involvement of ACE2 and Toll-like receptors (TLRs).

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Section: Ace2 Biology and Physiological Functionsmentioning

confidence: 99%

COVID-19-Induced Myocarditis: Pathophysiological Roles of ACE2 and Toll-like Receptors

Pannucci

Jefferson

Hampshire

et al. 2023

IJMS

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“…On the one hand, ACE2 transforms Ang II to Ang 1-7 with an anti-inflammatory nature. On the other hand, ACE2 is a binding receptor and entry route for SARS-CoV-2 [6,8,9]. Since the findings of experimental studies indicated that ACEI/ARB increased cellular membrane-bound ACE2 (mACE2) expression, opinions have emerged about whether ACEI/ARB may heighten susceptibility to SARS-CoV-2 infection and worsen its prognosis; thus, the justification of renin-angiotensin system (RAS) inhibition in COVID-19 patients was addressed [10].…”

Section: Sars-cov-2 Ang II Ang 1-7 Interactionmentioning

confidence: 99%

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: potential allies in the COVID-19 pandemic instead of a threat?

Šimko

Baka

2021

Clinical Science

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Angiotensin-converting enzyme 2 (ACE2) is the leading player of the protective renin–angiotensin system (RAS) pathway but also the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAS inhibitors seemed to interfere with the ACE2 receptor, and their safety was addressed in COVID-19 patients. Pedrosa et al. (Clin. Sci. (Lond.) (2021), 135, 465–481) showed in rats that captopril and candesartan up-regulated ACE2 expression and the protective RAS pathway in lung tissue. In culture of pneumocytes, the captopril/candesartan-induced ACE2 up-regulation was associated with inhibition of ADAM17 activity, counterbalancing increased ACE2 expression, which was associated with reduced SARS-CoV-2 spike protein entry. If confirmed in humans, these results could become the pathophysiological background for justifying RAS inhibitors as cornerstone cardiovascular protectives even during COVID-19 pandemic.

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“…In children or adolescent cohorts, where existence of confusing factors (i.e., epigenetic alterations) is lower, boys but not girls showed association of rs2158083, rs233575 and rs2074192 with hypertension ( 12 , 13 ). Nowadays, regulation of the ACE2 expression and activity has become essential for Coronavirus disease (COVID)-19 subjects, particularly for those with cardiovascular complications ( 6 , 14 ). Thus, further studies analyzing ACE2- SNPs and related haplotypes in young populations, could suggest predictive markers for CV diseases and molecular targets for CV therapy.…”

Section: Introductionmentioning

confidence: 99%

Association of ACE2 Polymorphisms and Derived Haplotypes With Obesity and Hyperlipidemia in Female Spanish Adolescents

Lumpuy‐Castillo

Vales-Villamarín²,

Mahíllo‐Fernández³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundIn the cardiovascular (CV) system, overactivation of the angiotensin converting enzyme (ACE) may trigger deleterious responses derived from angiotensin (Ang)-II, which can be attenuated by stimulation of ACE2 and subsequent Ang-(1-7) metabolite. However, ACE2 exhibits a high degree of genetic polymorphism that may affect its structure and stability, interfering with these cardioprotective actions. The aim of this study was to analyse the relationship of ACE2 polymorphisms with cardiovascular risk factors in children.MethodologyFive ACE2-single nucleotide polymorphisms (SNP), rs4646188, rs2158083, rs233575, rs879922, and rs2074192, previously related to CV risk factors, were analyzed in a representative sample of 12–16-year-old children and tested for their potential association with anthropometric parameters, insulin levels and the lipid profile.ResultsGirls (N = 461) exhibited lower rates of overweight, obesity, blood pressure, and glycemia than boys (N = 412), though increased plasma lipids. The triglycerides (TG)/HDL-C ratio was, however, lower in females. Interestingly, only in girls, the occurrence of overweight/obesity was associated with the SNPs rs879922 [OR 1.67 (1.02–2.75)], rs233575 [OR 1.98 (1.21- 3.22)] and rs2158083 [OR 1.67 (1.04–2.68)]. Also, TG levels were linked to the rs879922, rs233575, and rs2158083 SNPs, and the TG/HDL-C ratio was associated with rs879922 and rs233575. Levels of TC and LDL-C were associated with rs2074192 and rs2158083. Furthermore, the established cut-off level for TG ≥ 90 mg/dL was related to rs879922 [OR 1.78 (1.06–2.96)], rs2158083 [OR 1.75 (1.08–2.82)], and rs233575 [OR 1.62 (1.00–2.61)]. The cut-off level for TC ≥ 170 mg/dL was associated with rs2074192 OR 1.54 (1.04–2.28) and rs2158083 [OR 1.53 (1.04–2.25)]. Additionally, the haplotype (C-G-C) derived from rs879922-rs2158083-rs233575 was related to higher prevalence of overweight/obesity and TG elevation.ConclusionThe expression and activity of ACE2 may be essential for CV homeostasis. Interestingly, the ACE2-SNPs rs879922, rs233575, rs2158083 and rs2074192, and the haplotype (C-G-C) of the three former could induce vulnerability to obesity and hyperlipidemia in women. Thus, these SNPs might be used as predictive biomarkers for CV diseases and as molecular targets for CV therapy.

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ACE2, a multifunctional protein – from cardiovascular regulation to COVID-19

Cited by 8 publications

References 29 publications

COVID-19-Induced Myocarditis: Pathophysiological Roles of ACE2 and Toll-like Receptors

COVID-19-Induced Myocarditis: Pathophysiological Roles of ACE2 and Toll-like Receptors

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: potential allies in the COVID-19 pandemic instead of a threat?

Association of ACE2 Polymorphisms and Derived Haplotypes With Obesity and Hyperlipidemia in Female Spanish Adolescents

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