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

Heart Vessels. 2020 Feb;35(2):153-161. doi: 10.1007/s00380-019-01478-y. Epub 2019 Jul 29.

Abstract

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.

Keywords: Angiotensin-(1–7); Angiotensin-(1–9); Angiotensin-converting enzyme 2; Coronary heart disease; Renin angiotensin system.

MeSH terms

  • Aged
  • Angiotensin I / blood*
  • Angiotensin-Converting Enzyme 2
  • Biomarkers / blood
  • Coronary Angiography
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Stenosis / blood*
  • Coronary Stenosis / diagnostic imaging
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Peptidyl-Dipeptidase A / blood*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / blood*
  • Receptors, G-Protein-Coupled / blood*
  • Risk Factors
  • Sex Factors

Substances

  • Biomarkers
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)