ABSTRACT

Vascular smooth muscle cell (SMC) accumulation is a significant feature of cardiovascular diseases such as hypertension, atherosclerosis, and restenosis after angioplasty (Folkow, 1990; Schwartz et al., 1995). A primary determinant of vascular mass is the arterial media’s total DNA content, which is itself determined in large part by the balance between SMC DNA synthesis and degradation. Because DNA replication is reversible by cell death only, vascular growth associated with SMC DNA replication represents a mode of remodeling that is less readily reversible than vascular growth associated with protein or lipid accumulation without de novo DNA synthesis in arterial cells. Thus, the DNA content of the vessel wall (due to SMC hyperplasia or polyploidy) may be considered a record of past episodes of vascular growth, contributing to the persistence of the vascular disease. Apoptosis is an ubiquitous and highly regulated form of programmed cell death that is involved in tissue morphogenesis and homeostasis as the essential counterpart of cell replication (Thompson, 1995; Haunstetter and Izumo, 1998). In this context, apoptosis is potentially involved in the regulation of vascular remodeling, via the deletion of SMC in the vessel wall (Hamet et al., 1996; deBlois et al., 1997a). The

significance of apoptosis has been acknowledged in various fields of physiopathology, including, for instance, cancer, degenerative diseases, teratogenesis, or immune system regulation (Thompson, 1995). In this review, we discuss recent findings on the pharmacological regulation of SMC apoptosis in vivo and its potential significance for vascular wall remodeling in vascular diseases, with an emphasis on hypertension.