Najjar Rami S, Hekmatyar Nedumangalam, Wang Yanling, Ngo Vu, Lail Hannah L, Tejada Juan P, Danh Jessica P, Wanders Desiree, Feresin Rafaela G, Mehta Puja K, Gewirtz Andrew T
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Advanced Translational Imaging Facility, Georgia State University, Atlanta, GA 30303, USA.
bioRxiv. 2025 Aug 6:2025.04.19.649660. doi: 10.1101/2025.04.19.649660.
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.
We compared 28- and 40-week-old female normotensive Wistar-Kyoto and spontaneously hypertensive (SHR) rats, maintained, from age 4 weeks, on a control refined diet or a PBD, comprised of 28% fruits, vegetables, nuts and legumes. A subset of control SHRs were switched to the PBD at 28 weeks. CMD was assessed by coronary flow reserve via echocardiogram. Cardiac microvascular endothelial function was assessed via cMRI. Endothelial and VSMC function were assessed in the left ventricle (LV) 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.
SHRs exhibited endothelial dysfunction and likely VSMC dysfunction. PBD did not ameliorate their hypertension but, nonetheless, prevented and reversed CMD. PBD's mitigation of CMD was associated with improved endothelial nitric oxide synthase function and NO-mediated VSMC signaling, as well as reductions in LV oxidative stress, inflammatory signaling, and fibrosis. PBD altered the gut microbiota, although antibiotic studies failed to establish its importance in ameliorating CMD.
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.
冠状动脉微血管功能障碍（CMD）与不良心血管结局相关。CMD由内皮细胞和血管平滑肌细胞（VSMC）功能障碍驱动。我们旨在测试在高血压动物模型中，植物性饮食（PBD）是否可减轻CMD。
我们比较了28周龄和40周龄的雌性正常血压Wistar-Kyoto大鼠和自发性高血压（SHR）大鼠，从4周龄开始，分别维持在对照精制饮食或PBD上，PBD由28%的水果、蔬菜、坚果和豆类组成。一部分对照SHR在28周时改为PBD。通过超声心动图评估冠状动脉血流储备来评估CMD。通过心脏磁共振成像（cMRI）评估心脏微血管内皮功能。在左心室（LV）或分离的VSMC中评估内皮细胞和VSMC功能。通过16S测序和抗生素探究肠道微生物群的作用。还探讨了心脏炎症、氧化应激和纤维化。
SHR表现出内皮功能障碍，可能还有VSMC功能障碍。PBD并未改善它们的高血压，但尽管如此，预防并逆转了CMD。PBD对CMD的缓解与内皮型一氧化氮合酶功能改善、NO介导的VSMC信号传导改善以及LV氧化应激、炎症信号传导和纤维化减少有关。PBD改变了肠道微生物群，尽管抗生素研究未能证实其在改善CMD中的重要性。
PBD可预防SHR中CMD的发展并逆转已形成的CMD。PBD的这种益处发生在未减轻高血压的情况下，可能是由于内皮功能改善以及可能的VSMC功能改善。这些结果支持在人类CMD中测试PBD的临床试验。
