Georgia Elgohary

Background: Coronary microvascular dysfunction (CMD) is any abnormality of the structure and/or function of the microvasculature of coronary circulation¹. Risk factors for CMD are similar to those for coronary artery disease, namely chronic hypertension. High pressure in the large coronary arteries places stress on the microvessels, resulting in microvascular remodeling and endothelial function impairment². By disrupting normal endothelial function, decreased production of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) leads to ischemia and presentation of angina, dyspnea on exertion, and exercise intolerance^1,4. Currently, effective treatment for CMD is not available; most conditions are treated like obstructive CAD with mixed and undesirable results¹. Diagnosis of CMD has also proven difficult, as assessment of coronary endothelial tissue requires strictly invasive testing methods¹. Recent animal studies suggest plant-based diets may prevent and reverse hypertension-induced endothelial damage³.

Objective: In this review, mechanisms by which improvements to endothelial function by dietary habits were explored.

Search Methods: An online search in the Google Scholar database was conducted from 2019 to 2026 using the keywords “coronary microvascular disease”, “diet”, “hypertension”, and “endothelial function”.

Results: Studies indicated that a plant-based diet treated and reversed hypertension-induced CMD in rats^3,5. Coronary flow reserve depends on normal function of endothelial tissue, which demonstrated restoration after treatment with dietary changes. Additionally, coronary vessels showing hypertension-induced endothelial damage and reduced coronary blood flow demonstrated normal blood flow after a plant-based diet treatment^3,5. Implementation of a Mediterranean diet also promoted normal endothelial function8. Patients with an established history of coronary heart disease, both obstructive and nonobstructive, showed improved flow-mediated dilation, increased circulating endothelial progenitor cells, decreased circulating endothelial microparticles, and negative EMP/EPC ratios⁸. Expression of genes responsible for maintenance and function of endothelial cells may be altered by dietary choices⁶. Additionally, upregulation of inflammatory pathways, including TNF, NF-kB, NOD-like receptors, and IL-17, and downregulation of antioxidant and anti-inflammatory pathways, such as TGF-b, P13K-Akt, and VEGF, were present in the damaged endothelium⁶. Anthocyanins, present in several fruits and vegetables, induces gene expression for eNOS, nitric oxide, tretinoin, raloxifene, and ESR1⁷. Increased nitric oxide levels after treatment with anthocyanin extracts demonstrate improvement in endothelial function. Hypertension induces phenotypic changes in endothelium, rendering the tissue unable to maintain its normal structure and function⁶. Endothelial cells begin to acquire a mesenchymal phenotype in the presence of stressors, including hypertension⁶. To withstand the stress environment, endothelium alters its normal function and structure.

Conclusion: Hypertension induces endothelial damage that is characterized by remodeling and loss of function. Dietary habits may play a role in maintaining normal endothelial function by promoting eNOS gene expression, maintain a pan-endothelial phenotype, and maintain normal endothelial structure. Additionally, changes in diet may promote healing processes in endothelium after damage induced by chronic hypertension.

Works Cited:

1. Vancheri F, Longo G, Vancheri S, Henein M. Clinical Medicine Coronary Microvascular Dysfunction. J Clin Med. 2020;9(9).
2. Zdravkovic M, Popadic V, Klasnja S, et al. Coronary Microvascular Dysfunction and Hypertension: A Bond More Important than We Think. Medicina (Lithuania). 2023;59(12). doi:10.3390/medicina59122149
3. Najjar RS, Hekmatyar N, Wang Y, et al. Prevention and Reversal of Hypertension-Induced Coronary Microvascular Dysfunction by a Plant-Based Diet. Journal of the American Heart Association . 2025;14(22). doi:10.1161/JAHA.125.045515
4. da Silva GM, da Silva MC, Nascimento DVG, et al. Nitric oxide as a central molecule in hypertension: Focus on the vasorelaxant activity of new nitric oxide donors. Biology (Basel). 2021;10(10). doi:10.3390/biology10101041
5. Najjar RS, Mehta PK, Gewirtz AT. A Plant-Based Diet Prevented Coronary Microvascular Dysfunction (CMD) Independent of Hypertension in a Similar Manner to Gut Microbiota Depletion. Current Developments in Nutrition. 2024;8:102592. doi:https://doi.org/10.1016/j.cdnut.2024.102592
6. Li H, Jia Y, Chen Z, et al. Bioinformatics analysis of coronary microvascular dysfunction in rats based on single-cell RNA sequencing. Scientific Reports. 2025;15(1). doi:https://doi.org/10.1038/s41598-025-85318-2
7. Horie K, Naoki Nanashima, Maeda H. Phytoestrogenic Effects of Blackcurrant Anthocyanins Increased Endothelial Nitric Oxide Synthase (eNOS) Expression in Human Endothelial Cells and Ovariectomized Rats. 2019;24(7):1259-1259. doi:https://doi.org/10.3390/molecules24071259
8. Yubero-Serrano EM, Fernandez-Gandara C, Garcia-Rios A, et al. Mediterranean diet and endothelial function in patients with coronary heart disease: An analysis of the CORDIOPREV randomized controlled trial. PLoS Medicine. 2020;17(9). doi:https://doi.org/10.1371/journal.pmed.1003282