Microvascular Endothelial Dysfunction in Patients with Obesity

Abstract

Purpose of Review To examine the state of the art on the pathogenesis of endothelial dysfunction in the microcirculation of patients with obesity, focusing on the complex relationship between the consolidated and the novel mechanisms involved in this alteration.Recent Findings Human obesity is associated with vascular endothelial dysfunction, caused by a reduced nitric oxide availability secondary to an enhanced oxidative stress production. Pro-inflammatory cytokine generation, secreted by perivascular adipose tissue, is a major mechanism whereby obesity is associated with a reduced vascular NO availability. Vasculature also represents a source of low-grade inflammation and oxidative stress which contribute to endothelial dysfunction in obese patients. Recently, a direct influence of arginase on endothelial function by reducing nitric oxide availability was demonstrated in small vessels from patients with severe obesity. This effect is modulated by ageing and related to the high levels of vascular oxidative stress. Summary Oxidative stress, inflammation, and enzymatic pathways are important players in the pathophysiology of obesityrelated vascular disease. The identification of new therapeutic approaches able to interfere with these mechanisms will result in more effective prevention of the cardiovascular complications associated with obesity.

Relationship of Visceral Adipose Tissue With Dilated Perivascular Spaces

“…Also, males tend to accumulate fat at the visceral depot at any age ( Matsuzawa et al, 1995 ) which causes males to have more VAT than females. Moreover, as previously discussed, VAT, as an endocrine organ ( Wajchenberg, 2000 ), had more negative effects than SAT, which may lead to vascular endothelial damage ( Virdis et al, 2019 ).…”

“…In addition, animal studies provide some insight on the potential impact of obesity on the occurrence of CSVD. For example, a previous study ( Virdis et al, 2019 ) suggested that the pathology of endothelial dysfunction caused by obesity might be related to oxidative stress, inflammation, or enzyme-mediated pathways and may later manifest as CSVD. Interestingly, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) have different effects on disease formation ( Gil et al, 2011 ).…”

Tipping the scales: Are females more at risk for obesity‐ and high‐fat diet‐induced hypertension and vascular dysfunction?

“…Studies in both experimental animals and humans have identified the loss of NO as a central feature associated with the development of HFD‐ and obesity‐induced vascular dysfunction (Damjanovic & Barton, ; Engin, ; Virdis et al, ). There are also established sex differences in the NO/NOS pathway, making this an attractive potential mechanism to explain sex differences in vascular function.…”

The Effect of Low-Carbohydrate Diet on Macrovascular and Microvascular Endothelial Function Is Not Affected by the Provision of Caloric Restriction in Women with Obesity: A Randomized Study

“…The function and structure of these vasculatures are different: The macrovasculature buffers the increases in blood flow pulsatility, preventing tissue injury, and distributes blood to the body, whereas the microvasculature regulates vascular tone/resistance and blood pressure. In adults with obesity, endothelium-dependent vasodilation in both macro- and micro-vasculature are impaired [ 7 , 8 ].…”