Platelet Activation and Immune Phenotype Associate with the Degree of Adiposity and Hypertension during Obesity

Obesity is a chronic inflammatory disease associated with increased cardiometabolic risk. Platelets have emerged as important regulators of immune responses, including through antigen presentation and expression of co-signaling molecules. However, the impact of platelet immune phenotype on obesity remains unclear. We evaluate the expression of HLA class I, co-stimulatory, and co-inhibitory molecules on platelets in patients with obesity. Platelets were isolated from obese and eutrophic individuals, stimulated with suboptimal (0.05 U/mL) or optimal (0.5 U/mL) concentrations of thrombin, and analyzed by flow cytometry for HLA class I, CD40, CD80, CD86, and PD-L1 (CD274) expression. The study was approved by the IRB (5.736.117). No significant differences were observed between obese and eutrophic individuals when obesity was analyzed as a single group. However, stratification by obesity severity based on body mass index (BMI) revealed increased CD40 expression in class I and increased CD80 expression in class II–III obesity compared to controls. Following suboptimal thrombin stimulation, individuals with class II–III obesity exhibited higher CD80 and PD-L1 expression than those with class I obesity, suggesting that higher BMI may be associated with a platelet immune-regulatory phenotype in response to activation. Stratification by hypertension also revealed distinct phenotypes. Obese hypertensive individuals showed higher baseline expression of HLA class I, CD86, and PD-L1 than normotensive obese individuals. Following thrombin stimulation, hypertensive patients also exhibited increased CD40 and CD274 expression compared to normotensive individuals. These findings suggest that obesity severity and hypertension differentially shape the platelet immune phenotype, potentially contributing to chronic low-grade inflammation, cardiometabolic risk and immunosuppression associated with obesity.

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