Distinct inflammatory pathways shape atherosclerosis in different vascular beds

Abstract

Studies suggest varying atherosclerotic cardiovascular disease (ASCVD) prevalence across arterial beds. Factors such as smoking expedite ASCVD progression in the abdominal aorta, while diabetes accelerates plaque development in lower limb arteries, and hypertension plays a significant role in ASCVD development in the coronary and carotid arteries. Moreover, superficial femoral atherosclerosis advances slower compared with atherosclerosis in coronary and carotid arteries. Furthermore, femoral atherosclerosis exhibits higher levels of ossification and calcification, but lower cholesterol concentrations compared with atherosclerotic lesions of other vascular beds. Such disparities exemplify the diverse progression of ASCVD across arterial beds, pointing towards differential mechanistic pathways in each vascular bed. Hence, this review summarizes current literature on immune-inflammatory mechanisms in various arterial beds in ASCVD to advance our understanding of this disease in an aging society with increased need of vascular bed and patient-specific treatment options.

Keywords: Atherosclerosis; Calcification; Cardiovascular disease; Carotid; Coronary; Femoral arteries; Inflammation.

Graphical Abstract

Diverse embryonic origin and heterogeneous atherosclerotic lesions in different vascular beds. VAT, vascular adipose tissue.

Figure 1

Overview of the most prominent differences in human atherosclerotic lesions in different vascular beds. (A) Schematic drawing of an arterial wall and general characteristics of progressing atherosclerotic cardiovascular disease in cross sections of an arterial vessel. (B) A human being with arterial tree and heart. Individual arteries are named in black while embryonic origin of vascular smooth muscle cells is added in colour underneath and corresponds to the colour of the respective arterial section of the tree. Boxes left and right summarize individual lesion characteristics of each bed and are framed in the colour of vascular smooth muscle cell origin. In addition, thoracic and pericardial vascular adipose tissues are indicated. ASCVD, atherosclerotic cardiovascular disease; CAD, coronary artery disease; EC, endothelial cell; IL, interleukin; MACE, major adverse cardiovascular events; NF-κB nuclear factor-κB; siRNA, small interfering RNA, SMC, smooth muscle cell; TNF, tumour necrosis factor; tPVAT, thoracic periaortic vascular adipose tissue; VAT, vascular adipose tissue; VSMC, vascular smooth muscle cell; Mϕ, macrophage. Figure was made with Biorender.com