Vascular Dysfunction in Diabetes and Hypertension: Insights into HSP70

Diabetes and hypertension are closely interlinked and among the most prevalent diseases that significantly increase cardiovascular risks. They can be caused by a wide range of factors, which often affect overlapping molecular pathways, resulting in vascular dysfunction. Hyperglycemia in diabetes and increased angiotensin II levels in hypertension act similarly to promote vascular dysfunction by triggering pathways leading to oxidative stress, low-grade inflammation, and vessel remodeling. In this context, Heat Shock Protein 70 (HSP70), a ubiquitous molecular chaperone that exists locally (iHSP70) and systemically (eHSP70) and has opposing biological effects, is emerging as a new component associated with vascular dysfunction in chronic conditions. While elevated levels of eHSP70 in diabetes and hypertension have been associated with low-grade inflammation, iHSP70 appears to regulate intracellular calcium handling-a hallmark mechanism disrupted in both pathologies. This review focuses on the role of HSP70 as an evolving component of the intricate mechanisms underlying vascular dysfunction in these two pervasive diseases, which are very likely to coexist and represent a growing burden worldwide, while addressing whether HSP70 actively contributes to the vascular dysfunction or reflects an adaptive response to disease-associated stress across tissues and experimental models. Finally, we discuss emerging evidence on the pharmacological modulation of HSP70 and the challenges remaining in defining its role as a biomarker and therapeutic target.