Angiotensin-Converting Enzyme Gene D/I Polymorphism in Relation to Endothelial Function and Endothelial-Released Factors in Chinese Women

Abstract

Many studies have investigated the relationship between angiotensin-converting enzyme (ACE) D/I polymorphism and cardiovascular disease or endothelial dysfunction; however, hardly any of these studies has taken aging or menopause into consideration. Furthermore, despite that many studies have examined the regulatory effects of endothelial-released factors (ERFs) on endothelial function, no study has evaluated the relationship between ERFs and endothelial function with respect to ACE D/I polymorphism and menopause status. To answer these questions, 391 healthy Chinese women over a wide range of ages (22-75 years) were enrolled and divided into premenopause group and post-menopause group. After ACE D/I genotype being identified, the women were then classified into either DI/II or DD genotype. Flow-mediated dilatation (FMD) of brachial endothelium and plasma levels of ERFs: nitric oxide (NO), endothelin-1 (ET-1), and angiotensin II (Ang II) were measured. The results showed that frequencies of ACE D/I genotypes were in accordance with the Hardy-Weinberg equilibrium, and the frequency of I allele was higher than D allele. In pre-menopause group, FMD was significantly higher in women of DI/II than DD (P = 0.032), and agedependent in both genotypes (DD, P = 0.0472; DI/II, P < 0.0001). In post-menopause group, FMD was similar between women of DI/II and DD, and age-dependent only in women of DI/II (P < 0.0001). In pre-menopause group, Ang II level was significantly higher in women of DD than DI/II (P = 0.029), and FMD was significantly correlated with all ERFs in women of DD (NO, P = 0.032; ET-1, P = 0.017; Ang II, P = 0.002), but only with Ang II in women of DI/II (P = 0.026). In post-menopause group, no significant difference was observed in any ERF between women of DI/II and DD, and FMD was only significantly correlated with ET-1 in women of DD (P = 0.010). In summary, FMD in women of DI/II was superior to DD in pre-menopause and more age-dependent than DD in post-menopause, and FMD was closely associated with ERFs. In conclusion, Chinese women of DI/II seem to have lower risk than DD in pre-menopause, but similar risk as DD in post-menopause in developing cardiovascular disease.

Enalapril Is Superior to Lisinopril in Improving Endothelial Function without a Difference in Blood–Pressure–Lowering Effects in Newly Diagnosed Hypertensives

“…There appears to be selective targeting of the tissular ACE population linked to endothelial dysfunction by the lipophilic enalapril. This is in accordance with findings correlating vascular ACE inhibition (measured by changes in angiotensin peptide levels) [32] or vascular ACE expression (determined by genetic polymorphism) [33] with endothelial function. Moreover, the inhibition of ACE (and type 1 angiotensin 2 receptor) is associated with better endothelial function than that in patients treated with calcium channels or beta receptor blockers [31,34].…”

The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level

“…Several studies have reported associations between ACE gene polymorphisms (insertion/deletion) and cardiovascular diseases, including endothelial dysfunction, atherosclerosis, and heart failure [ 14 , 15 , 16 ]. The ACE I/D polymorphism has been linked to plasma ACE activity [ 17 , 18 ].…”

GJD Modulates Cardiac/Vascular Inflammation and Decreases Blood Pressure in Hypertensive Rats

“…We observed that GJD-HD had the largest decrease in SBP and DBP after six weeks of treatment. Angiotensin II and endothelin-1 are the main vasoconstrictors in hypertension pathogenesis [24][25][26]. Moreover, numerous studies found that increased Ang II and ET-1 activated NF-κB signaling pathway [27][28][29][30].…”