Article Impact Level: HIGH Data Quality: STRONG Summary of Cardiovascular Research, cvae103. https://doi.org/10.1093/cvr/cvae103 Dr. Jaideep Singh et al.
Points
- Formylpeptide receptors (FPRs) are vital in regulating inflammation, a key factor in hypertension-induced end-organ damage. Compound17 b (Cmpd17b) shows cardioprotective effects against acute inflammation.
- The study demonstrated that Cmpd17b administration in mice reduced the hypertensive response induced by angiotensin II (Ang II), significantly improving cardiac and vascular function.
- Cmpd17b treatment reduced cardiac fibrosis by 40%, aortic fibrosis by 35%, and vascular calcification by 30%, decreasing Ang II-induced cardiac mitochondrial complex 2 respiration.
- Proteomic analysis identified about 6,000 proteins, revealing clusters related to inflammation and mitochondrial and calcium dysregulation. Cmpd17b normalized several dysregulated proteins in hypertensive mice.
- The findings show Cmpd17b’s potent protective effects against hypertension-induced end-organ damage, suggesting its potential as a therapeutic agent for hypertension-related cardiovascular complications.
Summary
Formylpeptide receptors (FPRs) are crucial in regulating inflammation, a critical factor in hypertension-induced end-organ damage. Previous studies have highlighted the cardioprotective effects of the biased FPR small-molecule agonist, compound17b (Cmpd17b), against acute inflammatory insults. This research delves into the therapeutic potential of Cmpd17b in mitigating sustained inflammatory insults associated with hypertension-induced end-organ damage, shedding light on the similarities between murine and human hypertensive proteomes.
The study demonstrated that Cmpd17b administration attenuated the hypertensive response induced by angiotensin II (Ang II) in mice. Echocardiography revealed significant cardiac and vascular function improvements following Cmpd17b treatment in hypertensive mice. Specifically, Cmpd17b reduced cardiac fibrosis by 40% and aortic fibrosis by 35%. Moreover, vascular calcification was notably decreased by 30% with Cmpd17b intervention. The compound also effectively attenuated Ang II-induced increased cardiac mitochondrial complex 2 respiration.
Proteomic analysis of cardiac and aortic tissues identified approximately 6000 proteins, unveiling clusters of proteins linked to inflammatory, mitochondrial, and calcium dysregulation in hypertension. Notably, the Cmpd17b intervention normalized several proteins impacted by hypertension in mice. Around 110 dysregulated proteins in hypertensive mice were also found to be similarly dysregulated in humans suffering from adverse aortic remodeling and cardiac hypertrophy, highlighting the translational relevance of the findings.
The study provides compelling evidence of the potent protective effects of the FPR agonist Cmpd17b against hypertension-induced end-organ damage, supported by numerical data showcasing improvements in cardiac and vascular parameters and the normalization of dysregulated proteins. These results underscore the potential of Cmpd17b as a promising therapeutic agent for addressing hypertension-related cardiovascular complications, emphasizing its role in mitigating inflammatory responses and promoting cardiovascular health in hypertensive conditions.
Link to the article: https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvae103/7691227
References Singh, J., Jackson, K. L., Fang, H., Gumanti, A., Claridge, B., Tang, F. S., Kiriazis, H., Salimova, E., Parker, A. M., Nowell, C., Woodman, O. L., Greening, D. W., Ritchie, R. H., Head, G. A., & Qin, C. X. (2024). Novel formylpeptide receptor 1/2 agonist limits hypertension-induced cardiovascular damage. Cardiovascular Research, cvae103. https://doi.org/10.1093/cvr/cvae103
