Federal Project Grant Award Summary

Vanderbilt University Medical Center received an $883,216 Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), effective May 1, 2026 through February 28, 2030. The award supports basic and translational research investigating the pathophysiological role of mitochondrial cyclophilin D (CypD) acetylation in vascular dysfunction and hypertension. The research will define cell-specific mechanisms of endothelial and smooth muscle CypD-K166 acetylation in hypertension, test therapeutic interventions including novel CypD blockers and mitochondrial-targeted scavengers of isolevuglandins, and evaluate whether targeted reduction of CypD acetylation can rescue vascular function and reduce hypertension and end-organ damage.

This research addresses a significant clinical need, as approximately half of American adults have hypertension and 30 percent of hypertensive patients remain uncontrolled despite existing pharmacological treatments. The project advances a novel therapeutic paradigm by investigating CypD acetylation as a pathogenic gain-of-function mechanism, rather than pursuing global CypD depletion approaches that have demonstrated off-target effects in clinical trials. Research outputs will include characterization of disease mechanisms, identification of novel therapeutic targets, and pre-clinical validation of candidate interventions to inform future drug development and clinical translation.