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.