Relationship between circulating levels of angiotensin-converting enzyme 2-angiotensin-(1–7)-MAS axis and coronary heart disease

• Published in: Heart and vessels Vol. 35; no. 2; pp. 153 - 161
• Main Authors: Zhou, Xiaomin, Zhang, Ping, Liang, Tao, Chen, Yongyue, Liu, Dan, Yu, Huimin
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.02.2020; Springer Nature B.V
• Subjects: ACE2; Aged; Angiography; Angiotensin; Angiotensin I - blood; Angiotensin-Converting Enzyme 2; Arteriosclerosis; Atherosclerosis; Biomarkers - blood; Biomedical Engineering and Bioengineering; Blood vessels; Cardiac Surgery; Cardiology; Cardiovascular disease; Cardiovascular diseases; Coronary Angiography; Coronary artery disease; Coronary Artery Disease - blood; Coronary Artery Disease - diagnostic imaging; Coronary Stenosis - blood; Coronary Stenosis - diagnostic imaging; Enzyme-Linked Immunosorbent Assay; Enzymes; Female; Females; Health risk assessment; Heart diseases; Humans; Lesions; Male; Males; Medicine; Medicine & Public Health; Middle Aged; Original; Original Article; Peptide Fragments - blood; Peptidyl-Dipeptidase A - blood; Proto-Oncogene Proteins - blood; Receptors, G-Protein-Coupled - blood; Regression analysis; Renin; Risk Factors; Sex Factors; Subgroups; Trinucleotide repeats; Vascular Surgery; Angiotensin-(1–9); Renin angiotensin system; Angiotensin-converting enzyme 2; Angiotensin-(1–7); Coronary heart disease
• ISSN: 0910-8327; 1615-2573
• DOI: 10.1007/s00380-019-01478-y

As a counter-regulatory arm of the renin angiotensin system (RAS), the angiotensin-converting enzyme 2-angiotensin-(1–7)-MAS axis (ACE2-Ang-(1–7)-MAS axis) plays a protective role in cardiovascular diseases. However, the link between circulating levels of ACE2-Ang-(1–7)-Mas axis and coronary atherosclerosis in humans is not determined. The object of present study was to investigate the association of circulating levels of ACE2, Ang-(1–7) and Ang-(1–9) with coronary heart disease (CHD) defined by coronary angiography (CAG). 275 patients who were referred to CAG for the evaluation of suspected CHD were enrolled and divided into two groups: CHD group (diameter narrowing ≥ 50%, n  = 218) and non-CHD group (diameter narrowing < 50%, n  = 57). Circulating ACE2, Ang-(1–7) and Ang-(1–9) levels were detected by enzyme-linked immunosorbent assay (ELISA). In females, circulating ACE2 levels were higher in the CHD group than in the non-CHD group (5617.16 ± 5206.67 vs. 3124.06 ± 3005.36 pg/ml, P  = 0.009), and subgroup analysis showed the significant differences in ACE2 levels between the two groups only exist in patients with multi-vessel lesions ( P  = 0.009). In multivariate logistic regression, compared with the people in the lowest ACE2 quartile, those in the highest quartile had an OR of 4.33 (95% CI 1.20–15.61) for the CHD ( P for trend = 0.025), the OR was 5.94 (95% CI 1.08–32.51) for the third ACE2 quartile and 9.58 (95% CI 1.61–56.95) for the highest ACE2 quartile after adjusting for potential confounders ( P for trend = 0.022). However, circulating Ang-(1–7) and Ang-(1–9) levels had no significant differences between the two groups. In males, there were no significant differences in the levels of ACE2-Ang-(1–7)-MAS axis between two groups. Together, circulating ACE2 levels, but not Ang-(1–7) and Ang-(1–9) levels, significantly increased in female CHD group when compared with non-CHD group, increased ACE2 was independently associated with CHD in female and in patients with multi-vessel lesions even after adjusting for the confounding factors, indicating that ACE2 may participate as a compensatory mechanism in CHD.