scholarly journals Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 211 ◽  
Author(s):  
Swayam Prakash Srivastava ◽  
Julie E. Goodwin ◽  
Keizo Kanasaki ◽  
Daisuke Koya
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renal Fibrosis ◽  
Enzyme Inhibitors ◽  
Cultured Cells ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Critical Event ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Tgfβ Signaling ◽  
Converting Enzyme Inhibitors

Two class of drugs 1) angiotensin-converting enzyme inhibitors (ACEis) and 2) angiotensin II receptor blockers (ARBs) are well-known conventional drugs that can retard the progression of chronic nephropathies to end-stage renal disease. However, there is a lack of comparative studies on the effects of ACEi versus ARB on renal fibrosis. Here, we observed that ACEi ameliorated renal fibrosis by mitigating DPP-4 and TGFβ signaling, whereas, ARB did not show. Moreover, the combination of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), one of the substrates of ACE, with ACEi slightly enhanced the inhibitory effects of ACEi on DPP-4 and associated-TGFβ signaling. Further, the comprehensive miRome analysis in kidneys of ACEi+AcSDKP (combination) treatment revealed the emergence of miR-29s and miR-let-7s as key antifibrotic players. Treatment of cultured cells with ACEi alone or in combination with AcSDKP prevented the downregulated expression of miR-29s and miR-let-7s induced by TGFβ stimulation. Interestingly, ACEi also restored miR-29 and miR-let-7 family cross-talk in endothelial cells, an effect that is shared by AcSDKP suggesting that AcSDKP may be partially involved in the anti-mesenchymal action of ACEi. The results of the present study promise to advance our understanding of how ACEi regulates antifibrotic microRNAs crosstalk and DPP-4 associated-fibrogenic processes which is a critical event in the development of diabetic kidney disease.

Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on pulmonary function in hypertensive patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Azza S. Jabbar ◽  
Nadheera F. Neamah ◽  
Ahmed H. Al-Darraji
Keyword(s):  
Angiotensin Ii ◽  
Adverse Effects ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Hypertensive Patients ◽  
Receptor Blockers

Abstract Objectives Hypertension is a very common cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are widely used to treat hypertension. Many patients with hypertension are vulnerable to the antihypertensive adverse effects, which potentially reduces the adherence rate. Therefore, we conducted this study in order to evaluate the safety profile of both classes (ACEi and ARBs) on respiratory functions. Methods Two main groups of subjects were studied: first group is healthy control subjects and the second group is hypertensive patients, which was subdivided into subgroups in order to investigate the effect of all tested medications (captopril, enalapril, lisinopril, losartan, and valsartan). Respiratory efficiency was evaluated by measuring pulmonary function tests: FEV1, FVC, and FEV1%. Measurements were done using micromedical spirometer. Results We found that ARBs do not impair normal respiratory functions as measured by FEV1, FEV1%, and FVC in hypertensive patients. While ACEi treatments significantly reduced FEV1, FEV1%, and FVC compared to the other groups. Conclusions ARBs are not associated with any harmful effects on respiratory functions in hypertensive patients, unlike ACEi. As such, they could represent a first-choice treatment for hypertensive patients who are at high risk to the respiratory adverse effects.

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