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| Item Type: | Article |
|---|---|
| Title: | Angiotensin receptor-neprilysin inhibitor improves coronary collateral perfusion |
| Creators Name: | Li, K., Kratzmann, V., Dai, M., Gatzke, N., Rocic, P., Bramlage, P., Grisk, O., Lubomirov, L.T., Hoffmeister, M., Lauxmann, M.A., Ritter, O., Buschmann, E., Bader, M., Persson, A.B., Buschmann, I. and Hillmeister, P. |
| Abstract: | BACKGROUND: We investigated the pleiotropic effects of an angiotensin receptor-neprilysin inhibitor (ARNi) on collateral-dependent myocardial perfusion in a rat model of coronary arteriogenesis, and performed comprehensive analyses to uncover the underlying molecular mechanisms. METHODS: A rat model of coronary arteriogenesis was established by implanting an inflatable occluder on the left anterior descending coronary artery followed by a 7-day repetitive occlusion procedure (ROP). Coronary collateral perfusion was measured by using a myocardial particle infusion technique. The putative ARNi-induced pro-arteriogenic effects were further investigated and compared with an angiotensin-converting enzyme inhibitor (ACEi). Expression of the membrane receptors and key enzymes in the natriuretic peptide system (NPS), renin-angiotensin-aldosterone system (RAAS) and kallikrein-kinin system (KKS) were analyzed by quantitative polymerase chain reaction (qPCR) and immunoblot assay, respectively. Protein levels of pro-arteriogenic cytokines were measured by enzyme-linked immunosorbent assay, and mitochondrial DNA copy number was assessed by qPCR due to their roles in arteriogenesis. Furthermore, murine heart endothelial cells (MHEC5-T) were treated with a neprilysin inhibitor (NEPi) alone, or in combination with bradykinin receptor antagonists. MHEC5-T proliferation was analyzed by colorimetric assay. RESULTS: The in vivo study showed that ARNis markedly improved coronary collateral perfusion, regulated the gene expression of KKS, and increased the concentrations of relevant pro-arteriogenic cytokines. The in vitro study demonstrated that NEPis significantly promoted MHEC5-T proliferation, which was diminished by bradykinin receptor antagonists. CONCLUSION: ARNis improve coronary collateral perfusion and exert pro-arteriogenic effects via the bradykinin receptor signaling pathway. |
| Keywords: | Angiotensin Receptor-Neprilysin Inhibitor, Angiotensin-Converting Enzyme Inhibitor, Kallikrein-Kinin System, Heart Failure, Myocardial Infarction, Coronary Collateral Perfusion, Arteriogenesis, Animals, Mice, Rats |
| Source: | Frontiers in Cardiovascular Medicine |
| ISSN: | 2297-055X |
| Publisher: | Frontiers Media SA |
| Volume: | 9 |
| Page Range: | 981333 |
| Date: | 3 February 2023 |
| Official Publication: | https://doi.org/10.3389/fcvm.2022.981333 |
| PubMed: | View item in PubMed |
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