Interplay between Oxidative Stress and Inflammation in Cardiometabolic Syndrome

Around 50–60% of adults in western countries are either overweight or obese with more than 25% falling into the obese category [1]. The metabolic imbalance underlying obesity has fueled the prevalence of cardiometabolic syndrome— a constellation of interrelated risk factors of metabolic origins that together promote the increased risk of cardiovascular disease (CVD) and type II diabetes [2]. These are the major causes of morbidity, mortality, and sky-rocketing healthcare costs in industrialized countries. Obesity is the hallmark component of cardiometabolic syndrome with other key components being insulin resistance, hypertension, dys-lipidemia, and endothelial dysfunction. While each of the associated conditions has an independent effect, their clustering has a synergistic effect, making the risk of developing cardiovascular disease greater. Obesity with the associated cardiometabolic syndrome components has a direct effect on atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose and promotes proinflammatory and prothrombotic states. Cardiometabolic syndrome is associated with increased oxidative stress; however, the source of reactive oxygen species (ROS) and their exact targets are not well understood. Oxidation products of different organic molecules including lipids, proteins, and nucleic acids have been used to demonstrate the presence of oxidative stress in patients with cardiometabolic syndrome and CVD. Mitochondria have been shown to be a major source and target of reactive oxygen species in obesity-induced heart disease with consequences being impaired cardiac energetics, development of left ventricular hypertrophy, and diastolic dysfunction [3]. Angiotensin II-induced activation of NADPH oxidase also plays a role, with direct effects via redox posttranslational modifications of proteins within the caveolar compartment. The further downstream effects of ROS and redox regulation are mediated mostly by protein oxidative and nitrosative posttranslational modifications of proteins [4]. Cardiometabolic syndrome has also been associated with the presence of a number of inflammatory markers. Low-grade inflammation is a common manifestation and could play a role in the pathogenesis of obesity and cardiometabolic syndrome and its sequelae. Dysregulation of adipose tissue biology plays a potential role in the initiation of inflammatory events in obesity and cardiometabolic syndrome causing chronic inflammatory response characterized by abnormal adipokine production and the activation of several proin-flammatory signaling pathways, resulting in the induction of several proinflammatory cytokines from adipose tissue that have been suggested to play a role in pathogenesis of CVD. Furthermore, the dysregulation adipose tissue biology, mediated by increased redox stress and inflammation, adversely affects angiogenesis both locally and systemically [5], further contributing to the global impact …