Endothelial Dysfunction in Obesity and Therapeutic Targets

Area of Science:

• Cardiovascular Science
• Metabolic Disease Research
• Endocrinology

Background:

• Rising global obesity rates correlate with increased cardiovascular disease mortality.
• Obesity-induced chronic inflammation and dysregulated adipokines impair vascular homeostasis, leading to endothelial dysfunction.
• Key factors include adipose tissue inflammation, reduced nitric oxide (NO) bioavailability, insulin resistance (IR), and oxidized low-density lipoproteins (oxLDLs).

Purpose of the Study:

• To explore the mechanisms of obesity-related endothelial dysfunction.
• To identify therapeutic targets for cardiovascular protection in obese individuals.
• To evaluate the efficacy of novel pharmacological interventions.

Main Methods:

• Analysis of perivascular adipose tissue (PVAT) changes in obesity.
• Investigation of adipocyte-exosome-macrophage crosstalk.
• Assessment of clinical markers like leptin, irisin, and remnant cholesterol.
• Evaluation of therapeutic agents including liraglutide, empagliflozin, and metformin.

Main Results:

• Obesity alters PVAT, promoting inflammation, oxidative stress, and pro-atherogenic macrophage phenotypes.
• Liraglutide improves vascular function via a cAMP-independent PKA-AMPK pathway in PVAT.
• Empagliflozin (EMPA) and metformin alleviate endothelial dysfunction and oxidative stress, but lack comprehensive anti-inflammatory effects.
• GLP-1 receptor agonists and bariatric surgery demonstrate potential for vascular repair and cardiometabolic risk improvement.

Conclusions:

• Obesity-driven endothelial dysfunction is a critical factor in cardiorenal metabolic syndrome and type 2 diabetes progression.
• Targeting specific pathways, such as arginase activity or GLP-1 agonism, offers therapeutic potential.
• Current treatments for obesity-related diabetes have limitations in simultaneously addressing inflammation and endothelial dysfunction.