Atherosclerosis: Implications of Angiotensin II and the AT-1 Receptor

Summary

Atherosclerosis is a chronic inflammatory disease of the arterial intima. It is associated with the accumulation of monocytes, monocyte-derived macrophages, macroph-age-derived foam cells, T-lymphocytes, and a sparse number of mast cells. Inflammation is the body’s natural, protective response to injury. Paradoxically, this complex process of repair and healing can become destructive. This leads to fibrosis and scarring, with the eventual loss of the vital functions of the organs or tissues involved. In the atherosclerotic process, we see an extensive inflammatory infiltrate, which leads to plaque instability and its vulnerability to rupture.

Atherosclerosis is a fibroproliferative disease associated with the accumulation of collagen and extracellular matrix synthesized by the smooth muscle cell. The smooth muscle cell, so important and damaging in the early phase of atherosclerosis, paradoxically becomes the cell type so protective in stabilizing the vulnerable plaque in the later stages of this disease process. It may be referred to as the “sentinel” of the fibrous cap.

The driving force behind the atherosclerotic process is the retention of modified low-density lipoproteins.

As this inflammatory-fribroproliferative disease progresses, a custom delivery system of microvessels develops within the arterial wall, which supplies the necessary substrates to fuel this inflammatory, destructive process, called the “vasa vasorum”.

In this chapter, the role of angiotensin (Ang) II and its receptor AT₁ is discussed. Their relation to the development, progression, and final fate of the atherosclerotic plaque and how they relate to cardiovascular disease cannot be overemphasized.