Biomarkers of Oxidative Stress Tethered to Cardiovascular Diseases

Abstract

Cardiovascular disease (CVD) is a broad term that incorporated a group of conditions that affect the blood vessels and the heart. CVD is a foremost cause of fatalities around the world. Multiple pathophysiological mechanisms are involved in CVD; however, oxidative stress plays a vital role in generating reactive oxygen species (ROS). Oxidative stress occurs when the concentration of oxidants exceeds the potency of antioxidants within the body while producing reactive nitrogen species (RNS). ROS generated by oxidative stress disrupts cell signaling, DNA damage, lipids, and proteins, thereby resulting in inflammation and apoptosis. Mitochondria is the primary source of ROS production within cells. Increased ROS production reduces nitric oxide (NO) bioavailability, which elevates vasoconstriction within the arteries and contributes to the development of hypertension. ROS production has also been linked to the development of atherosclerotic plaque. Antioxidants can decrease oxidative stress in the body; however, various therapeutic drugs have been designed to treat oxidative stress damage due to CVD. The present review provides a detailed narrative of the oxidative stress and ROS generation with a primary focus on the oxidative stress biomarker and its association with CVD. We have also discussed the complex relationship between inflammation and endothelial dysfunction in CVD as well as oxidative stress-induced obesity in CVD. Finally, we discussed the role of antioxidants in reducing oxidative stress in CVD.

Figure 1

Schematic representation and molecular mechanism of the sources of ROS generation in CVD. Mitochondria is the leading cause of ROS generation; complexes I and III produce superoxides and open mPTP pores in the mitochondrial membrane through ROS release. NOX2/gp91phox generates O^2•, and other members of the NOX1, NOX4, and NOX5 family are known to be involved in ROS generation. Xanthine oxidase accepts an electron from O² and produces O^2• while its action can be blocked by allopurinol. Lipoxygenase produces ROS by acting on arachidonic acid into HETE, and LOXBlock-1 blocks this step. When eNOS is uncoupled, it forms O₂^• instead of NO and helps in ROS production. MPO is the critical oxidative stress biomarker that reacts with H₂O₂ and produces various super radicals, which are the primary source of ROS.

Figure 2

Schematic representation of the primary mechanisms involved in endothelial dysfunction in CVD. Endothelial cell rich in eNOS enzyme that produces NO is an essential compound in the endothelial function. eNOS acts on the cGMP pathway in VSMC and causes vasodilation. When eNOS is uncoupled, it reduces NO's production, which leads to decreased vasodilation properties and causes endothelial dysfunction. Oxidative stress is enhanced during aging, elevating the release of cytokines and ROS production; these act on the vascular wall and cause inflammation. Mental stress in CVD reduces eNOS mRNA expression and decreases BH4 activity, enhancing ROS generation and reducing NO bioavailability. OXLDL levels are high during atherosclerosis and increase the release of the ET-1 vasoconstrictor, which is also a significant factor of endothelial dysfunction. Other CVD risk factors like smoking, hypertension, and hypercholesterolemia generate ROS, causing inflammation and ultimately leads to endothelial dysfunction.