Myocardial perfusion recovery induced by an α-calcitonin gene-related peptide analogue

Abstract

Background Endogenous calcitonin gene-related peptide (CGRP) induces cardioprotective effects through coronary vasodilation. However, the systemic administration of CGRP induces peripheral vasodilation and positive chronotropic and inotropic effects. This study aims to examine the net effect on coronary perfusion of the systemically administered α-calcitonin gene-related peptide analogue, SAX, in rats during myocardial infarction. Methods Forty Sprague-Dawley rats underwent myocardial infarction. Following left anterior descending artery occlusion, [99mTc]Tc-sestamibi was administered to determine the myocardial perfusion before treatment. Twenty minutes, 24 and 48 h after [99mTc]Tc-sestamibi injection, the rats were treated with either SAX or placebo. Final infarct size was determined three weeks later by [99mTc]Tc-sestamibi SPECT/CT scan. Results Thirty-one rats survived the surgery and 20 completed the follow-up SPECT/CT scan (SAX n = 12; Placebo n = 8). At baseline, there was no difference in size of perfusion defect between the groups (P = .88), but at follow-up the SAX group had improved myocardial recovery compared to the placebo group (P = .04), corresponding to a relative perfusion recovery of 55% in SAX-treated rats. Conclusion The CGRP analogue, SAX, has a cardioprotective effect in this rat model of myocardial infarction, improving myocardial perfusion recovery after chronic occlusion of the coronary artery.

CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells and its pulmonary levels correlate with viral clearance in critical COVID-19 patients

“…Next, Calu-3 cells were pre-treated for 24h at 37°C with CGRP within its concentration range that inhibits LCs-mediated HIV-1 and HSV-1/2 infection, as we reported (29,30). The cells were also pre-treated with the CGRP metabolically stable analogue SAX (serinyl-CGRP 2-37amide with an albumin binding fatty acid moiety in the N-terminus) that, like CGRP, exerts protective cardiovascular effects (37)(38)(39)(40) and anti-viral functions (29,30), as we reported. The cells were next washed, pulsed with SARS-CoV-2 variants for 4h, and infection was determined by flow cytometry as above.…”

Alpha-Calcitonin Gene Related Peptide: New Therapeutic Strategies for the Treatment and Prevention of Cardiovascular Disease and Migraine

“…Researchers demonstrated that subcutaneous administration of acylated-α-CGRP significantly reduced cardiac hypertrophy, fibrosis, and inflammation, and improved cardiac function in these disease rodent models. Recently, the cardioprotective effect of a metabolically stable CGRP analog, SAX, has been tested in a constant left anterior descending (LAD) occlusion rat model of acute myocardial infarction (Bentsen et al, 2021). Researchers reported that intraperitoneal administration of SAX (100 nmole/kg bwt per rat) improved myocardial recovery after myocardial infarction.…”