Effects of Bariatric Surgery on Cardiovascular Risk Profile in Relation to Inflammatory Parameters: Endothelial Phenotyping and Analysis of the Cross-talk Between Adipose Tissue and Endothelium

The pathogenesis of obesity is multifactorial, involving dietary, socioeconomic, genetic, and metabolic factors. The accumulation of adipose tissue-especially abdominal fat-is only one aspect of the disease. Visceral fat, in fact, produces pro-inflammatory cytokines (adipocytokines) that contribute to the local recruitment of activated inflammatory macrophages (known as M1). These cells progressively accumulate in the adipose tissue and further amplify the inflammatory response.

Endothelial dysfunction, defined as the inability of the endothelium to regulate key vascular functions (such as vasodilation, coagulation, and permeability), is considered the earliest pathological event leading to atherosclerosis. In obesity, systemic inflammation, adipose tissue dysfunction, oxidative stress, and the presence of other risk factors contribute to impaired endothelial homeostasis-events that occur well before clinically evident cardiovascular (CV) disease.

Bariatric surgery has proven effective not only in reducing body weight but also in improving obesity-related comorbidities, particularly those involving the cardiovascular system. The hypothesis that weight loss also restores endothelial homeostasis-by interrupting the positive inflammatory feedback loop driven by fat accumulation-is supported by recent literature. However, the timing of functional recovery, as well as the influence of individual differences and cardiovascular risk factors on this process, remains unclear. Moreover, the mechanisms underlying adipose tissue-endothelium interactions are still only partially understood.This experimental project aims to study the cardiovascular and metabolic impact of obesity, and how this changes in response to the drastic weight loss induced by bariatric surgery.

Specifically, we plan to analyze endothelial homeostasis and adipose tissue dysfunction in these patients, in order to detect subclinical vascular alterations and explore potential mechanisms of cross-talk between adipocytes and the endothelium.

Our central hypothesis is that obesity leads to altered endothelial homeostasis, driven by mediators released from adipose tissue and by changes in the gut microbiota. We expect that, at 6 and 12 months after surgery-and with adequate weight loss-there will be progressive resolution of endothelial dysfunction, along with a reduction in circulating adipose-specific mediators and inflammatory markers, ultimately leading to a significant improvement in overall cardiovascular risk profile.