Increased Gene Expression of Nuclear Factor PPARγ Through Exercise and Use of Modulator Drugs May Reduce Risk of Coronary Artery Disease
Emaan Hassan
Background: The heart is made up of three layers: epicardium, myocardium, and endocardium. Epicardial adipose tissue (EAT) is the accumulation of adipose tissue between the epicardium and myocardium.[1] EAT surrounds major coronary vessels and is in close relation to the cardiomyocytes in the myocardial layer. EAT shares the same vasculature as myocardiocytes. Abnormal levels may increase inflammation in the blood vessels and impact the endothelial cells.[3] Coronary artery disease (CAD) is one of the leading causes of morbidity globally and is caused by accumulation of fat deposits in coronary vessels.[2] To determine the presence of CAD, a thorough history and physical examination must be done. Risk factors such as family history, past medical history of a heart attack and or stroke, smoking, and environmental factors play an important role.[1] CAD is linked to increased levels of cholesterol. Therefore, patients who have a family history of hypercholesterolemia are at a higher risk of developing CAD. Patients may present to the clinic with shortness of breath, angina, and myocardial infarction.[4] Preventative measures such as lifestyle changes and maintaining a healthy diet are key to managing the disease progression; however, scientific research has been looking into drug therapies which can help patients with CAD. Nuclear factors PPARγ, LXRβ, and RORα are being studied due to their role in metabolism and can therefore be potential targets for combatting CAD.[2]
Objective: In this literature review we will look into the mechanism of nuclear factor PPARγ and how gene expression level of PPARγ mitigates CAD. We will also explore ways to prevent CAD and possible drug therapies.
Search Methods: A PubMed search was done narrowing the search to papers within the past five years focusing on cardiovascular disease and epicardial adipose tissue.
Results: Literature review indicated that PPARγ mRNA levels were decreased in obese patients with CAD and women with metabolic syndrome[4]. Exercise was shown to alleviate symptoms and increase PPARγ mRNA levels[5]. Additionally, drug therapy with Pemafibrate and Atorvastatin ester have been shown to improve the regulation of PPARγ mRNA levels[6,7].
Conclusions: Several research articles focused on abdominal obesity and liver function. This is an indication that there is still much research to be done on cardiovascular disease and on the treatment and prevention of coronary artery disease. Cardiovascular disease is tied to familial, dietary, and environmental factors, and these should be monitored before the disease progresses and leads to more serious complications. Dietary changes and exercise are key in prevention of CAD. However, drug therapies can be looked into, and, based on the literature review done, PPARγ plays a role in metabolic pathways, inflammation and adipogenesis.
Works Cited.
- Panteleeva AA, Razgildina ND, Pobozheva IA, et al. Expression of Genes Encoding Nuclear Factors PPARγ, LXRβ, and RORα in Epicardial and Subcutaneous Adipose Tissues in Patients with Coronary Heart Disease. Bull Exp Biol Med. 2021;170(5):654-657. doi:10.1007/s10517-021-05126-2
- Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 2019;234(10):16812-16823. doi:10.1002/jcp.28350
- Karampetsou N, Alexopoulos L, Minia A, et al. Epicardial Adipose Tissue as an Independent Cardiometabolic Risk Factor for Coronary Artery Disease. Cureus. 2022;14(6):e25578. Published 2022 Jun 1. doi:10.7759/cureus.25578
- Panteleeva AA, Razgildina ND, Brovin DL, et al. The Expression of Genes Encoding ABCA1 and ABCG1 Transporters and PPARγ, LXRβ, and RORα Transcriptional Factors in Subcutaneous and Visceral Adipose Tissue in Women with Metabolic Syndrome. Mol Biol (Mosk). 2021;55(1):64-74. doi:10.31857/S0026898421010134
- Zheng, F., & Cai, Y. (2019). Concurrent exercise improves insulin resistance and nonalcoholic fatty liver disease by upregulating PPAR-γ and genes involved in the beta-oxidation of fatty acids in ApoE-KO mice fed a high-fat diet. Lipids in health and disease, 18(1), 6. https://doi.org/10.1186/s12944-018-0933-z
- Hu N, Chen C, Wang J, Huang J, Yao D, Li C. Atorvastatin Ester Regulates Lipid Metabolism in Hyperlipidemia Rats via the PPAR-signaling Pathway and HMGCR Expression in the Liver. Int J Mol Sci. 2021;22(20):11107. Published 2021 Oct 14. doi:10.3390/ijms222011107
- Das Pradhan A, Glynn RJ, Fruchart JC, et al. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk. N Engl J Med. 2022;387(21):1923-1934. doi:10.1056/NEJMoa2210645