A plant-based diet, atherogenesis, and coronary artery disease prevention

Abstract

A plant-based diet is increasingly becoming recognized as a healthier alternative to a diet laden with meat. Atherosclerosis associated with high dietary intake of meat, fat, and carbohydrates remains the leading cause of mortality in the US. This condition results from progressive damage to the endothelial cells lining the vascular system, including the heart, leading to endothelial dysfunction. In addition to genetic factors associated with endothelial dysfunction, many dietary and other lifestyle factors, such as tobacco use, high meat and fat intake, and oxidative stress, are implicated in atherogenesis. Polyphenols derived from dietary plant intake have protective effects on vascular endothelial cells, possibly as antioxidants that prevent the oxidation of low-density lipoprotein. Recently, metabolites of L-carnitine, such as trimethylamine-N-oxide, that result from ingestion of red meat have been identified as a potential predictive marker of coronary artery disease (CAD). Metabolism of L-carnitine by the intestinal microbiome is associated with atherosclerosis in omnivores but not in vegetarians, supporting CAD benefits of a plant-based diet. Trimethylamine-N-oxide may cause atherosclerosis via macrophage activation. We suggest that a shift toward a plant-based diet may confer protective effects against atherosclerotic CAD by increasing endothelial protective factors in the circulation while reducing factors that are injurious to endothelial cells. The relative ratio of protective factors to injurious endothelial exposure may be a novel approach to assessing an objective dietary benefit from a plant-based diet. This review provides a mechanistic perspective of the evidence for protection by a plant-based diet against atherosclerotic CAD.

Figure 1.

Potential plant-based diet targets to prevent coronary artery disease. A new look at the steps of atherogenesis paradigm takes into account new information on plant-based diets. A plant-based diet could be considered a medicine that prevents and treats atherogenesis by multiple pathways. A diet low in fat, low in cholesterol, low in salt, and low in red meat may decrease vascular endothelial cell (VEC) injury. Polyphenols may decrease oxidation of low-density lipoprotein (LDL) and prevent oxidized LDL (OxLDL)-induced monocyte adhesion to VEC, monocyte transformation into macrophages, and foam cell formation. Reducing red meat intake may decrease trimethylamine-N-oxide (TMAO) formation. Decreasing TMAO formation inhibits atherogenesis by down-regulating macrophage uptake of OxLDL. Because there is no direct way to measure atherogenesis, it may be necessary to continue to monitor LDL cholesterol and OxLDL levels, hypertension, and blood sugar levels. In the future, it may be possible to monitor substances such as polyphenols and TMAO that may help to identify patients at risk for atherogenesis before they actually progress to atherosclerosis, plaque rupture, and myocardial infarction.

Figure 2:

Proinflammatory gene expression and lifestyle modification. Figure 2 shows proinflammatory gene expression of 8 genes (see below) from individuals who completed a year-long lifestyle modification program that consisted of a low-fat vegetarian diet, 180 minutes of physical activity per week, and stress reduction classes. Compared with a matched control group, the participant group showed a validated differential reduction in gene expression of proinflammatory genes involved in neutrophil activation and molecular pathways important to vascular function.

1. Gene Symbol = Gene Name (Gene Ontology Biologic Process)

2. LTF = lactotransferrin (immune response)

3. LCN2 = lipocalin (transporter activity)

4. CEACAM8 = carcinoembryonic antigen-related (immune response)

5. CRISP3 = cysteine-rich secretory protein 3 (immune response; defense response)

6. HP = haptoglobin protein (defense response)

7. OLFM4 = olfactomedin4 (cell adhesion)

8. CAMP = cathelicidin antimicrobial peptide (defense response)

9. BPI = bactericidal/permeability-increasing protein (immune response; lipid binding)

1. Ellsworth DL, Croft DT, Weyandt J, et al. Intensive cardiovascular risk reduction induces sustainable changes in expression of genes and pathways important to vascular function. Circ Cardiovasc Genet 2014 Apr 1;7(2):151–60. DOI: http://dx.doi.org/10.1161/CIRCGENETICS.113.000121.