Cardiomyocyte-targeted HSP60 modulates myocardial remodeling pathways and peripheral blood mononuclear cell mitochondrial membrane potential in hypertensive diabetic rats

Arterial hypertension and diabetes mellitus frequently coexist and synergistically accelerate adverse left ventricular remodeling through mitochondrial dysfunction, sterile inflammation, and extracellular matrix disorganization. Heat shock protein 60 (HSP60) is a mitochondrial chaperone involved in proteostasis and stress adaptation, but it remains unclear whether cardiomyocyte-restricted augmentation of HSP60 can modulate myocardial remodeling and influence systemic immune-cell bioenergetics. Male spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats were studied with or without streptozotocin-induced diabetes. Animals were assigned to WKY, SHR, WKY+HSP60, SHR+HSP60, WKY + DM+HSP60, and SHR + DM+HSP60 groups. HSP60 was delivered using an adeno-associated virus serotype 9 (AAV9) vector under the cardiac troponin T promoter. Myocardial remodeling was assessed by histomorphometry and Masson’s trichrome staining, myocardial signaling by immunohistochemistry and RT-qPCR, and peripheral blood mononuclear cell (PBMC) mitochondrial membrane potential by JC-1 flow cytometry. Cardiac HSP60 delivery showed a context-dependent pattern. In hypertensive diabetic rats, this pattern included altered NLRP3 subcellular localization, modulation of mitochondrial regulatory and inflammatory-fibrotic transcripts, and increased PBMC mitochondrial membrane potential. PBMC polarization inversely correlated with myocardial fibrosis. Normotensive and single-pathology groups did not show a comparable integrated response profile. These findings indicate that cardiomyocyte-targeted HSP60 overexpression is associated with remodeling-related changes in myocardium and peripheral immune-cell bioenergetics under combined hypertensive and diabetic stress. PBMC mitochondrial membrane potential may represent a candidate peripheral indicator of myocardial state in this preclinical setting.