Vasodilator Dysfunction in Human Obesity: Established and Emerging Mechanisms.

Area of Science:

• Cardiovascular Science
• Metabolic Disease Research
• Vascular Biology

Background:

• Obesity is linked to insulin resistance, metabolic syndrome, and cardiovascular complications.
• Understanding obesity-related vascular dysfunction is crucial for clinical management.
• Complex interplay of pathophysiological mechanisms remains incompletely understood.

Purpose of the Study:

• To review alterations in intravascular homeostatic mechanisms in obese patients.
• To identify causative factors of obesity-related vasodilator dysfunction.
• To discuss emerging pathophysiological mechanisms and potential therapeutic strategies.

Main Methods:

• Review of current literature on obesity-related vascular dysfunction.
• Analysis of intravascular homeostatic alterations in obese arteries.
• Discussion of causative factors including insulin resistance, lipotoxicity, and adipose tissue abnormalities.

Main Results:

• Obesity disrupts vascular homeostasis through mechanisms like insulin resistance and lipotoxicity.
• Emerging factors include skeletal muscle inflammation, gut microbiome signals, extracellular vesicles, and microRNAs.
• Current knowledge gaps exist, but novel treatments are emerging.

Conclusions:

• Obesity-induced vascular dysfunction is multifactorial, involving known and emerging pathways.
• Early identification and personalized management are essential.
• Novel therapies like GLP-1 enhancers and SGLT2 inhibitors show promise in mitigating vascular complications.