Extracellular Vesicles and Renal Fibrosis: An Odyssey toward a New Therapeutic Approach

Renal fibrosis is a complex disorder characterized by the destruction of kidney parenchyma. There is currently no cure for this devastating condition. Extracellular vesicles (EVs) are membranous vesicles released from cells in both physiological and diseased states. Given their fundamental role in transferring biomolecules to recipient cells and their ability to cross biological barriers, EVs have been widely investigated as potential cell-free therapeutic agents. In this review, we provide an overview of EVs, focusing on their functional role in renal fibrosis and signaling messengers responsible for EV-mediated crosstalk between various renal compartments. We explore recent findings regarding the renoprotective effect of EVs and their use as therapeutic agents in renal fibrosis. We also highlight advantages and future perspectives of the therapeutic applications of EVs in renal diseases.     

Potential Role of Dipeptidyl Peptidase IV in the Pathophysiology of Heart Failure

Dipeptidyl peptidase IV (DPPIV) is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including glucagon-like peptide-1 (GLP-1), brain natriuretic peptide (BNP) and stromal cell-derived factor-1 (SDF-α), all of which play important roles in the cardiovascular system. In this regard, recent reports have documented that circulating DPPIV activity correlates with poorer cardiovascular outcomes in human and experimental heart failure (HF). Moreover, emerging evidence indicates that DPPIV inhibitors exert cardioprotective and renoprotective actions in a variety of experimental models of cardiac dysfunction. On the other hand, conflicting results have been found when translating these promising findings from preclinical animal models to clinical therapy. In this review, we discuss how DPPIV might be involved in the cardio-renal axis in HF. In addition, the potential role for DPPIV inhibitors in ameliorating heart disease is revised, focusing on the effects of the main DPPIV substrates on cardiac remodeling and renal handling of salt and water.