Endothelium and its alterations in cardiovascular diseases: life style intervention

Abstract

The endothelium, which forms the inner cellular lining of blood vessels and lymphatics, is a highly metabolically active organ that is involved in many physiopathological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion, and trafficking and inflammation. In this review, we summarized and described the following: (i) endothelial cell function in physiological conditions and (ii) endothelial cell activation and dysfunction in the main cardiovascular diseases (such as atherosclerosis, and hypertension) and to diabetes, cigarette smoking, and aging physiological process. Finally, we presented the currently available evidence that supports the beneficial effects of physical activity and various dietary compounds on endothelial functions.

Figure 1

The activation of endothelial nitric oxide synthase (eNOS) may be induced by shear stress, estrogens, or increase of intracellular Ca²⁺ concentration and may be inhibited, mainly during aging physiopathological process, by oxidative stress and reduction of Sirtuin 1 activity and of estrogens level. In healthy endothelium, eNOS plays multiple functions, such as nitric-oxide vasodilation and inhibition of platelet aggregation and may induce endothelial progenitor cells activation and functions.

Figure 2

Transient receptor potential channels (TRPCs) clustered around a central ion pore enabling influx of calcium and sodium ions. Ca²⁺: calcium; Na⁺: sodium.

Figure 3

Endothelial functions in physiological conditions. The net balance of endothelium-derived vasodilators and vasoconstrictors or anticoagulants and procoagulants along with inhibition of proinflammatory and oxidative stress factors release and leukocyte adhesion and transmigration maintain a healthy vascular homeostasis.

Figure 4

Main pathways activated during hyperglycaemia and low insulin level that alter the modulation of vascular tone, reducing nitric oxide, and increasing endothelin-1 release and so lead to endothelial dysfunction and diabetes-associated vascular disease. Cav-1: caveolin-1, eNOS: endothelial nitric oxide synthase; ET-1: endothelin-1; NO: nitric oxide.

Figure 5

Schematic representation of endothelial dysfunction induced by chronic exposure to nicotine.

Figure 6

Schematic summary of the main age-related endothelial alterations.

Figure 7

Potential atheroprotective role of Mediterranean diet during the atherogenetic process. The Mediterranean diet, with mainly its antioxidant properties, may (1) inhibit/reduce the imbalance between vasoconstrictors and vasodilators, (2) block oxidation of low density lipoproteins, (3) inhibit monocytes adhesion to endothelial cells constraining monocytes infiltration in the subendothelial space, (4) repress differentiation of macrophages in lipid-laden macrophages, defined as foam cells, and (5) reduce radical oxygen species syntheses. ET-1: endothelin-1; LDLs: low density lipoproteins; NO: nitric oxide; ROS: radical oxygen species.