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Prevention and Reversal of Hypertension‐Induced Coronary Microvascular Dysfunction by a Plant‐Based Diet

R. Najjar,Nedumangalam Hekmatyar,Yanling Wang,Vu L Ngo,Hanna Lail,Juan P. Tejada,Jessica P. Danh,Desiree Wanders,Rafaela G. Feresin,P. Mehta,Andrew T. Gewirtz

Published 2025 in Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease

ABSTRACT

Background Coronary microvascular dysfunction (CMD) is associated with adverse cardiovascular outcomes. CMD is driven by endothelial and vascular smooth muscle cell (VSMC) dysfunction. We aimed to test whether CMD could be mitigated by a plant‐based diet (PBD) in an animal model of hypertension. Methods We compared 28‐ and 40‐week‐old female normotensive Wistar–Kyoto and spontaneously hypertensive rats (SHRs), maintained, from age 4 weeks, on a control refined diet or a PBD, composed of 28% fruits, vegetables, nuts, and legumes. A subset of control SHRs was switched to the PBD at 28 weeks. CMD was assessed by coronary flow reserve via echocardiogram. Cardiac microvascular endothelial function was assessed via cardiac magnetic resonance imaging. Endothelial and VSMC function were assessed in the left ventricle or in isolated VSMCs. The role of gut microbiota was probed via 16S sequencing and antibiotics. Cardiac inflammation, oxidative stress, and fibrosis were also explored. Results SHRs exhibited endothelial dysfunction and likely VSMC dysfunction. A PBD did not ameliorate their hypertension but, nonetheless, prevented and reversed CMD. The PBD’s mitigation of CMD was associated with improved endothelial nitric oxide synthase function and nitric oxide–mediated VSMC signaling, as well as reductions in left ventricular oxidative stress, inflammatory signaling, and fibrosis. A PBD altered the gut microbiota, although antibiotic studies failed to establish its importance in ameliorating CMD. Conclusions A PBD prevented CMD development and reversed established CMD in SHRs. Such benefits of PBD, which occurred without alleviating hypertension, were possibly due to improved endothelial function and likely improved VSMC function. These results support clinical trials to test PBDs in human CMD.

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