Impact of obesity on the reparative potency of adipose-derived mesenchymal stem cells in hypertensive cardiomyopathy

Obesity constitutes a formidable risk factor for cardiovascular diseases; however, its implications for adipose tissue-derived mesenchymal stem cells (ADMSCs) in the context of hypertensive cardiomyopathy remain insufficiently elucidated. This investigation seeks to illuminate the effects of obesity on the reparative potential of ADMSCs extracted from both obese (O) and normal control (NC) mice within a hypertensive model, thereby addressing a critical void in current research. A model of hypertension (HT) was developed in C57BL/6J mice through the administration of angiotensin II (Ang II). In groups of Non-HT and HT animals, vehicles, NC or obese ADMSCs were injected intravenously. Left ventricular (LV) function in vivo was estimated by echocardiogram. Hypertensive cardiomyopathy was meticulously scrutinized by serum biochemical assays, histology, immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR). The serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified utilizing enzyme-linked immunosorbent assay (ELISA). The expression of autophagy-related and PI3K/AKT pathway related protein was investigated by western blotting. NC-ADMSCs but not O-ADMSCs normalized the Ang II induced elevated blood pressure and myocardial wall thickness. Both NC- and O-ADMSCs alleviated myocardial tissue damage in HT, but NC ADMSCs decreased oxidative stress and blunted myocardial microvascular rarefaction more effectively. Obese ADMSCs exhibited increased inflammation and pro-fibrosis level in vitro. The heart tissue of vehicle-injected HT mice had decreased ratio of p-mTOR to mTOR, P-PI3K to PI3K, and P-AKT to AKT, lower abundance of p62, higher level of ULK1 and Beclin 1, and elevated ratio of LC3II to LC3I compared to Non-HT animals, consistent with HT-associated promotion of autophagy. The changes were largely reversed in heart of NC-ADMSCs injected mice but partially alleviated in O-ADMSCs treating. Obese ADMSCs are less effective in protecting against Ang II induced myocardial hypertrophy in mice which might be partially relevant to its impaired regulation of autophagy through the PI3K/AKT axis.