Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Oxidative Stress (OS) is one of the pathophysiological mechanisms of CVDs such as hypertension, atherosclerosis, myocardial infarction (MI), ischemia reperfusion (I/R) injury, and heart failure. Resveratrol, a natural polyphenol compound has cardioprotective effects acting via several molecular mechanisms including reduction of OS in cardiovascular system. Our goal was to provide an updated overview of the pathophysiological role of OS in CVDs. Furthermore, we explored the cardiovascular effect of resveratrol and its mechanism of actions involved, especially focusing on its role as an antioxidant molecule in CVDs.
Methods: We searched through 50-60 original research and review articles using online databases (PubMed, science direct, google scholar). Research papers relevant to our review study published in the last 20 years, mainly using papers published in the last 5 years. Figures were created using Adobe illustrator.
Results: It has been shown that OS cause endothelial dysfunction leading to the CVDs. Reactive Oxygen Species (ROS) may lead to endothelial dysfunction by decreasing Nitrous Oxide (NO) through oxidizing an important cofactor tetrahydrobiopterin to trihydrobiopterin radical. This oxidation reaction leads to endothelial nitric oxide synthase uncoupling and induces free radical and superoxide generation that might lead to a multitude of CVDs. Endothelial dysfunction may cause inflammation, through cell signaling by TNFa, Angiotensin-II, and Endothelin-1. Endothelin-1 causes a positive feedback loop of increasing OS and is a key factor in vascular inflammation which is central for foam cell production, and lipid accumulation on arterial walls known as atherosclerosis. Atherosclerotic plaque rupture and subsequent formation of occlusive thrombi may induce MI. MI can also be induced by endothelial disruption of NO production that leads to platelet aggregation occluding blood vessel. Paradoxically, the reperfusion of ischemic or infarcted myocardium can lead to further injury, called I/R injury, that is characterized by induction of ROS. Excessive ROS activates autophagy, apoptotic and inflammatory pathways through Beclin-1, NLRP3 and MAPKs, respectively. This increases proapoptotic protein Bax while decreasing anti-apoptotic protein Bcl-2 which causes cardiomyocyte death, leading to heart failure.
Resveratrol has been found to have potential therapeutic effects in CVDs. The activation of SIRT1/ AMPK pathway helps regulate cardiomyocyte energy and cellular repair which contributes to the mitigation of hypertension by promoting vasodilation, reducing OS, and improving endothelial function. Inhibiting PI3K/Akt/mTOR prevents excessive vascular smooth muscle cell proliferation, a key factor in atherosclerosis development. Resveratrol's action in blocking TGF-β/Smad pathways may limit cardiac fibrosis, crucial in conditions like heart failure due to myocardial ischemia or MI-induced cardiac remodeling. Additionally, activation of Nrf2 pathway by resveratrol promotes antioxidant enzyme production and inhibits NADPH oxidase, alleviating OS associated with ischemia-reperfusion injury and MI.
Conclusion: OS is shown to be involved in the pathogenesis of several CVDs such as hypertension, atherosclerosis, ischemia reperfusion, MI, and heart failure. A natural antioxidant compound resveratrol has been shown to have potential as a therapeutic agent, to treat these CVDs. The beneficial cardiovascular effects of resveratrol may involve several molecular pathways such as SIRT1/AMPK, PI3K/Akt/mTOR, TGF- β/Smad, and Nrf2.
Academic/Professional Position
Medical Student
Mentor/PI Department
Medical Education
Recommended Citation
Sepulveda, Alyssa; Heckman, Justin Z.; Ochoa, Grace; and Shah, Amin, "Oxidative Stress, a culprit in cardiovascular diseases and Resveratrol as a potential therapeutic agent" (2024). Research Symposium. 57.
https://scholarworks.utrgv.edu/somrs/2024/posters/57
Non-HSR Determination Letter
Included in
Oxidative Stress, a culprit in cardiovascular diseases and Resveratrol as a potential therapeutic agent
Background: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Oxidative Stress (OS) is one of the pathophysiological mechanisms of CVDs such as hypertension, atherosclerosis, myocardial infarction (MI), ischemia reperfusion (I/R) injury, and heart failure. Resveratrol, a natural polyphenol compound has cardioprotective effects acting via several molecular mechanisms including reduction of OS in cardiovascular system. Our goal was to provide an updated overview of the pathophysiological role of OS in CVDs. Furthermore, we explored the cardiovascular effect of resveratrol and its mechanism of actions involved, especially focusing on its role as an antioxidant molecule in CVDs.
Methods: We searched through 50-60 original research and review articles using online databases (PubMed, science direct, google scholar). Research papers relevant to our review study published in the last 20 years, mainly using papers published in the last 5 years. Figures were created using Adobe illustrator.
Results: It has been shown that OS cause endothelial dysfunction leading to the CVDs. Reactive Oxygen Species (ROS) may lead to endothelial dysfunction by decreasing Nitrous Oxide (NO) through oxidizing an important cofactor tetrahydrobiopterin to trihydrobiopterin radical. This oxidation reaction leads to endothelial nitric oxide synthase uncoupling and induces free radical and superoxide generation that might lead to a multitude of CVDs. Endothelial dysfunction may cause inflammation, through cell signaling by TNFa, Angiotensin-II, and Endothelin-1. Endothelin-1 causes a positive feedback loop of increasing OS and is a key factor in vascular inflammation which is central for foam cell production, and lipid accumulation on arterial walls known as atherosclerosis. Atherosclerotic plaque rupture and subsequent formation of occlusive thrombi may induce MI. MI can also be induced by endothelial disruption of NO production that leads to platelet aggregation occluding blood vessel. Paradoxically, the reperfusion of ischemic or infarcted myocardium can lead to further injury, called I/R injury, that is characterized by induction of ROS. Excessive ROS activates autophagy, apoptotic and inflammatory pathways through Beclin-1, NLRP3 and MAPKs, respectively. This increases proapoptotic protein Bax while decreasing anti-apoptotic protein Bcl-2 which causes cardiomyocyte death, leading to heart failure.
Resveratrol has been found to have potential therapeutic effects in CVDs. The activation of SIRT1/ AMPK pathway helps regulate cardiomyocyte energy and cellular repair which contributes to the mitigation of hypertension by promoting vasodilation, reducing OS, and improving endothelial function. Inhibiting PI3K/Akt/mTOR prevents excessive vascular smooth muscle cell proliferation, a key factor in atherosclerosis development. Resveratrol's action in blocking TGF-β/Smad pathways may limit cardiac fibrosis, crucial in conditions like heart failure due to myocardial ischemia or MI-induced cardiac remodeling. Additionally, activation of Nrf2 pathway by resveratrol promotes antioxidant enzyme production and inhibits NADPH oxidase, alleviating OS associated with ischemia-reperfusion injury and MI.
Conclusion: OS is shown to be involved in the pathogenesis of several CVDs such as hypertension, atherosclerosis, ischemia reperfusion, MI, and heart failure. A natural antioxidant compound resveratrol has been shown to have potential as a therapeutic agent, to treat these CVDs. The beneficial cardiovascular effects of resveratrol may involve several molecular pathways such as SIRT1/AMPK, PI3K/Akt/mTOR, TGF- β/Smad, and Nrf2.