|Year : 2014 | Volume
| Issue : 1 | Page : 59-60
Angiotensin-converting enzyme inhibitors in lipid metabolism and atherosclerosis: An ace up the sleeve?
Department of Internal Medicine, Princess Durru Shehvar Children's and General Hospital, Puranahaveli, Hyderabad, India
|Date of Web Publication||7-Feb-2014|
Department of Internal Medicine, Princess Durru Shehvar Children's and General Hospital, Hyderabad
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gude D. Angiotensin-converting enzyme inhibitors in lipid metabolism and atherosclerosis: An ace up the sleeve?. J Sci Soc 2014;41:59-60
It is commonly believed that Angiotensin-converting enzyme inhibitors (ACEi) are lipid neutral. On the contrary, studies have shown that at least some ACEi could favorably improve lipid profile and atherosclerotic changes.
ACEi are known to increase HDL-cholesterol and decrease triglycerides. A study concluded that Angiotensin-converting enzyme (ACE) inhibition with benazepril reduces the atherogenic profile by decreasing lipoprotein and increasing HDL-cholesterol, the latter being correlated with reduction in microalbuminemia. When given along with amlodipine, benazapril showed similar trends in lipid sub-fractions apart from greater blood pressure lowering effect.  A randomized study on 104 patients with acute myocardial infarction showed that captopril therapy for seven years, significantly improved HDL levels along with benefits in cardiovascular events, heart failure and mortality.  In another observation, enalapril significantly reduced total cholesterol, TGs, VLDL-C, non-HDL-C, and TG to HDL-C ratio. 
ACEi are documented to slow down plaque formation in the progression of atherosclerosis in hyperlipidaemia. They decrease plaque cholesterol content and cellularity. Studies have shown that ACEi maintains normal endothelial function, with preserved vasodilatation response.  ACEi (specifically enalapril and zofenopril) have shown to increase circulating endothelial progenitor cells (EPC), prevented progression of vascular damage and demonstrated an inverse correlation between circulating EPC levels and intima media thickness values in newly diagnosed hypertensive patients.  Such pleiotropic effects of ACEi are believed to occur via improved lipid status, blockade of production of aldosterone and the conversion of angiotensin I to angiotensin II. ACEi are effective in prevention of endothelial dysfunction, progression of atherosclerosis and coronary artery events. Captopril is known to inhibit LDL oxidation, which is instrumental in development and progression of atherosclerosis. The sulfhydryl group on captopril may confer resistance to oxidation. 
A study compared atenolol to captopril and found that while treatment with the former resulted in significantly higher triglycerides and atherogenic index (AI), the latter resulted in significantly lower serum LDL and significant decrease of serum TG and AI along with significantly higher serum HDL-cholesterol.  The perindopril-thrombosis, inflammation, endothelial dysfunction and neurohormonal activation trial found that ACE inhibition with perindopril significantly lowered biomarkers of the atherothrombotic complications (D-dimer) and the pro-inflammatory cytokine TNF-α. 
In non-alcoholic steatohepatitis, therapy either with irbesartan or perindopril improves insulin sensitivity and reduces transaminases compared to controls (in animal models). They also resulted in a significant reduction in the immunostaining of TNF-α, IL-6 and TGF-β1 compared to controls.  ACEi affect adipocyte homeostasis via Cellular retinol binding protein-1 through the activation of retinoic acid receptor/RXR (retinoid X receptor)-peroxisome proliferator-activated receptor signaling and up-regulation of adiponectin. The latter may explain the delaying of type 2 diabetes by ACEi. 
On the other hand, the benefits in lipid profile up on ACEi treatment have not been universal. A study on normotensives concluded that enalapril and perindopril had no effect on plasma lipids although the latter significantly reduced plasma levels of oxidized LDLs, CRP (C-Reactive Protein), MCP-1, fibrinogen and PAI-1, and increased interleukin-10.  Another small study of perindopril in obese humans did not show any effect on blood lipids or flow-mediated dilation. 
As our understanding of ACEi continues to improve, important facets such as, effects on lipid profile bring to the forefront their mechanism against atherosclerosis and other cardiovascular benefits. There is an urgent need for larger scale randomized control trials to establish their stand in lipid metabolism.
| Acknowledgments|| |
I thank our colleagues and staff of the department of Internal medicine for their perpetual support.
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