Diabetes Progression Disrupts Endothelial Function Through Loss of Piezo1‑Dependent Vasorelaxation
Poster Number
64
Faculty Mentor Name
Roshanak Rahimian
Format
Poster Presentation
Research or Creativity Area
Pharmacy
Abstract
PIEZO1 is a mechanosensitive cation channel expressed throughout the vasculature that converts shear stress into calcium-dependent vasodilatory signals governing endothelial nitric oxide (NO) production and vascular tone. While impaired mechanotransduction is a recognized contributor to diabetic vascular dysfunction, the progression of PIEZO1 signaling deficits from prediabetes to overt diabetes remains poorly defined. We hypothesized that worsening metabolic status across the prediabetic–diabetic transition is linked to endothelial dysfunction and a selective loss of PIEZO1- mediated vasorelaxation in diabetes.
Purpose
Male Sprague–Dawley (SD) and UCD-T2DM rats (control, prediabetic, diabetic) underwent metabolic and hemodynamic characterization, including body weight, adiposity, fasting glucose, HbA1c, glucose tolerance, triglycerides, insulin, HOMA-IR, and blood pressure. Mesenteric arterial function was evaluated using wire myography to measure acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced relaxation, phenylephrine (PE)-induced contraction, and Yoda1-evoked PIEZO1-dependent relaxation with or without L-NAME. Piezo1, nitric oxide synthase 3 (Nos3), and guanylyl cyclase 1 subunits (Gucy1α1 and Gucy1β1) gene expression levels were measured by qPCR.
Results
Diabetic group exhibited reduced body weight and adiposity but marked elevations in fasting glucose, HbA1c, triglycerides, and blood pressure. Glucose intolerance was present in both diseased groups, with prediabetic rats showing elevated insulin and diabetic group had the highest HOMA-IR. ACh-induced vasorelaxation was impaired in prediabetic and diabetic arteries, with the lowest maximal relaxation observed in diabetics. PE-induced contraction was enhanced in diabetics, as indicated by increased sensitivity and maximal tension. Yoda1 relaxation was impaired only in diabetic rats; L-NAME caused a marked rightward shift in prediabetes but only a minimal shift in diabetes, indicating progressive loss of PIEZO1–NO signaling. SNP-induced relaxation was diminished in diabetics, suggesting smooth muscle dysfunction in this group. qPCR analyses demonstrated marked reductions in Piezo1 and Nos3 expression in diabetic arteries, decreased Nos3 in prediabetics, and downward trends in Gucy1α1 in diabetics, collectively reflecting progressive disruption of endothelial NO production and downstream cGMP signaling.
Significance
In conclusion, prediabetes to diabetes progression is characterized by worsening metabolic abnormalities, hypertension, and impaired endothelial NO-mediated vasorelaxation. Nos3 expression is reduced in prediabetes, reflecting early disruption of NO signaling, whereas PIEZO1- dependent relaxation remains intact until diabetes, where it becomes selectively impaired alongside reduced Piezo1 expression. This pattern suggests that early NO pathway dysfunction precedes overt loss of PIEZO1–NO mechanotransduction and identifies this axis as a potential therapeutic target in diabetic vascular disease.
Location
University of the Pacific, DeRosa University Center
Start Date
24-4-2026 11:00 AM
End Date
24-4-2026 2:00 PM
Diabetes Progression Disrupts Endothelial Function Through Loss of Piezo1‑Dependent Vasorelaxation
University of the Pacific, DeRosa University Center
PIEZO1 is a mechanosensitive cation channel expressed throughout the vasculature that converts shear stress into calcium-dependent vasodilatory signals governing endothelial nitric oxide (NO) production and vascular tone. While impaired mechanotransduction is a recognized contributor to diabetic vascular dysfunction, the progression of PIEZO1 signaling deficits from prediabetes to overt diabetes remains poorly defined. We hypothesized that worsening metabolic status across the prediabetic–diabetic transition is linked to endothelial dysfunction and a selective loss of PIEZO1- mediated vasorelaxation in diabetes.
Comments
Khadizatul Kobra will present the poster at the Research and Creativity Showcase on 24th April.