Endothelial dysfunction, platelet hyperactivity, hypertension, and the metabolic syndrome: molecular insights and combating strategies

Abstract

Metabolic syndrome (MetS) is a multifaceted condition that increases the possibility of developing atherosclerotic cardiovascular disease. MetS includes obesity, hypertension, dyslipidemia, hyperglycemia, endothelial dysfunction, and platelet hyperactivity. There is a concerning rise in the occurrence and frequency of MetS globally. The rising incidence and severity of MetS need a proactive, multipronged strategy for identifying and treating those affected. For many MetS patients, achieving recommended goals for healthy fat intake, blood pressure control, and blood glucose management may require a combination of medicine therapy, lifestyles, nutraceuticals, and others. However, it is essential to note that lifestyle modification should be the first-line therapy for MetS. In addition, MetS requires pharmacological, nutraceutical, or other interventions. This review aimed to bring together the etiology, molecular mechanisms, and dietary strategies to combat hypertension, endothelial dysfunction, and platelet dysfunction in individuals with MetS.

Keywords: atherosclerotic cardiovascular disease; endothelial dysfunction; hypertension; metabolic syndrome; platelet hyperactivity.

Figure 1

Insulin resistance due to oxidative stress is attributed to a disparity between the body’s antioxidant system and the generation of ROS, which in turn triggers inflammatory responses, atherosclerosis, hypertension, and myocardial infarction.

Figure 2

Risk factors of MetS.

Figure 3

The mechanisms underlying endothelial dysfunction. The endothelial cells undergo oxidative stress due to alterations in their extracellular matrix layers caused by various factors such as aging, genetic predisposition, and environmental variables. The principal sources of ROS are NADPH oxidase and uncoupled nitric oxide synthase (NOS). The occurrence of endothelial function is attributed to an elevation in ROS beyond the innate antioxidant capabilities of the body. In addition, the production of substantial amounts of hydrogen peroxide (H₂O₂) contributes to the impairment of endothelial function and consequent cellular death.

Figure 4

Illustration of a series of processes involved in the hypertension mechanism.

Figure 5

Thrombosis’s rapid spread due to circulating white blood cells and platelets. Endothelial cells release P-selectin through the exocytosis of Weibel Palade bodies (WPB) when stimulated by tumor necrosis factor alpha during inflammation. P-selectin glycoprotein ligand-1 (PSGL-1) recruits leukocytes such as neutrophils and monocytes by P-selectin. Neutrophil extracellular traps (NET) ensnare invaders, stimulate thrombus development, and activate platelets after being released by neutrophils. Platelets’ activation allows leukocytes to become activated and identify infections. Thrombus production is also encouraged by tissue factor (TF), which is released from the surface of monocytes and their microvesicles to initiate fibrin synthesis and red blood cell recruitment. The resultant thrombus aids in the entrapment of the infectious agent.