Vascular Diseases and Gangliosides

Abstract

Vascular diseases, such as myocardial infarction and cerebral infarction, are most commonly caused by atherosclerosis, one of the leading causes of death worldwide. Risk factors for atherosclerosis include lifestyle and aging. It has been reported that lifespan could be extended in mice by targeting senescent cells, which led to the suppression of aging-related diseases, such as vascular diseases. However, the molecular mechanisms underlying the contribution of aging to vascular diseases are still not well understood. Several types of cells, such as vascular (endothelial cell), vascular-associated (smooth muscle cell and fibroblast) and inflammatory cells, are involved in plaque formation, plaque rupture and thrombus formation, which result in atherosclerosis. Gangliosides, a group of glycosphingolipids, are expressed on the surface of vascular, vascular-associated and inflammatory cells, where they play functional roles. Clarifying the role of gangliosides in atherosclerosis and their relationship with aging is fundamental to develop novel prevention and treatment methods for vascular diseases based on targeting gangliosides. In this review, we highlight the involvement and possible contribution of gangliosides to vascular diseases and further discuss their relationship with aging.

Keywords: aging; atherosclerosis; ganglioside; inflammatory cells; senescence; vascular cells; vascular disease.

Figure 1

The process of atherosclerosis involving vascular and vascular-associated cells. Vascular cells, including endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, adipocytes from the intima, media, adventitia and perivascular adipose tissue (PVAT), and other inflammatory cells participate in the inflammatory process of atherosclerosis via multiple intricate pathways. Dysfunction of ECs, transformation of monocytes/macrophages into foam cells, migration, proliferation and dedifferentiation of smooth muscle cells (SMCs), transformation of fibroblasts into myofibroblasts, and production of adipokines by adipocytes in the PVAT are predominantly implicated in the pathological process of atherosclerosis. This process is characterized by the following steps: atheromatous plaque formation, plaque failure and thrombus formation.

Figure 2

Schematic diagram of GSL pathways. Pathways of the major gangliosides (a- and b-series) mentioned in this review are shown within the dotted rectangles. Glc, Glucose; Gal, Galactose; GalNAc, N-acetylgalactosamine; Neu5Ac, N-acetylneuraminic acid.

Figure 3

Possible involvement of gangliosides derived from aged and senescent cells in the onset and progression of age-related vascular diseases.