Abstract
Endothelium plays a fundamental role in the cardiovascular system, forming an interface between blood and adjacent tissues by regulating the vascular tone through the synthesis of nitric oxide, prostaglandins and other relaxing factors. Endothelial dysfunction is characterized by vasoconstriction, cell proliferation and shifting toward a proinflammatory and prothrombic state. In hypertension endothelial dysfunction may be involved in the initiation and development of vascular inflammation, vascular remodeling, and atherosclerosis and is independently associated with increased cardiovascular risk. Different conditions such as impaired vascular shear stress, inflammation and oxidative stress, activation of the renin angiotensin system have been described as important pathophysiological mechanisms involved in the development of endothelial dysfunction. The release of extracellular vesicles by neighboring cells in the vascular wall has emerged as an important regulator of endothelial function and with potential antihypertensive properties and beneficial effects by counteracting the hypertension mediated organ damage. Furthermore, macrovesicles are emerging as an innovative therapeutic approach for vascular protection, allowing the delivery of bioactive molecules, such as miRNA and drugs interacting with the renin angiotensin system. In this review we summarize the available evidence about the pathophysiological implications of endothelial dysfunction in cardiovascular diseases, focusing on hypertension and its sequelae, and the potential innovative therapeutic strategies targeting the endothelium with the aim to improve vascular function and remodeling.
Highlights
Frontiers in MedicineEndothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Front
Vascular endothelium plays an important role in cardiovascular (CV) physiology, forming an interface between blood and adjacent tissues and it is involved in nutrients and metabolites transport as well as in the interaction with circulating cells, hormones, and cytokines [1]
We have recently shown that angiotensin converting enzyme (ACE)-2/Ang [1,2,3,4,5,6,7]/MasR axis plays an important role in arterial protection during selective AT1R blockade through the improvement of endothelial function and remodeling of resistance arteries via the reduction of reactive oxygen species (ROS) production and increased nitric oxide (NO) bioavailability [54] (Figure 1)
Summary
Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Front. In hypertension endothelial dysfunction may be involved in the initiation and development of vascular inflammation, vascular remodeling, and atherosclerosis and is independently associated with increased cardiovascular risk. Different conditions such as impaired vascular shear stress, inflammation and oxidative stress, activation of the renin angiotensin system have been described as important pathophysiological mechanisms involved in the development of endothelial dysfunction. In this review we summarize the available evidence about the pathophysiological implications of endothelial dysfunction in cardiovascular diseases, focusing on hypertension and its sequelae, and the potential innovative therapeutic strategies targeting the endothelium with the aim to improve vascular function and remodeling
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