Aminoguanidine Induced Up-Regulation of Sphingosine-1 Phosphate Receptor-1 (S1PR1) in Heart Tissue of Diabetic Rats

 Cardiac microvascular complications are a significant concern in diabetes, often related to dysfunction of the sphingosine-1-phosphate receptor-1 (S1PR1). Aminoguanidine (AG) is recognized for its capability to alleviate these complications by inhibiting advanced glycation compounds and enhancing vascular function in diabetic rats. Therefore, this study seeks to investigate the therapeutic potential of AG by assessing its impact on the gene expression of S1PR1 in the heart tissue of diabetic rats.

 Thirty-four diabetic and healthy rats were stratified into eight groups, including diabetic rats, diabetic rats administered with varying doses of AG 50, 100, and 200 mg/kg, healthy rats treated with the same AG doses, and untreated healthy controls. RNA extraction and cDNA synthesis were performed using heart tissue samples, followed by real-time PCR analysis. The fold change in S1PR1 gene expression was then assessed and compared among diabetic rats treated with varying AG doses and their corresponding control groups.

The analysis demonstrated a significant reduction in S1PR1 gene expression in diabetic rats compared to controls. However, AG treatment improved S1PR1 expression, which was correlated with the administered dose, with a notable upregulation observed in rats treated with 200 mg/kg of AG compared to other groups (P<0.001).

 Considering the significance of the S1PR1 pathway in inhibiting microangiopathy, augmenting S1PR1 gene expression through AG treatment may hold promise in preventing diabetes-related cardiovascular complications.