THE TIME WINDOW OF APOPTOSIS - A NEW COMPONENT IN THE THERAPEUTIC STRATEGY FOR CARDIOVASCULAR REMODELING

Apoptosis and experimental hypertrophy Apoptosis (programmed cell deat h) is a physiological counterpart of cell replication with shared as w ell as specific pathways. Our initial studies have demonstrated increa sed apoptosis in the heart, kidney and brain of spontaneously hyperten sive rats (SHR) and mice, persisting in cultured vascular smooth muscl e cells. In these target organs of hypertension, programmed cell death paralleled the well known hypertrophy/hyperplasia. We also observed t hat the two processes can be dissociated in time, as in experimental h ypertrophy of the heart induced by pressure overload. In this context, only a short-lived apoptotic window precedes the overt development of cardiac hypertrophy. Effects in hypertension We now propose that a mo re prolonged apoptotic window is present in hypertension. Apoptosis se ems to be significantly reduced during the first weeks of life in SHR, possibly contributing to the early cardiac hyperplasia. However, incr eased apoptosis is clearly evident thereafter throughout the developme nt of hypertension and fades below the levels observed in normotensive animals after the age of 24 weeks. Antihypertensive therapy and apopt osis In addition to the apoptotic windows that suggest a dynamic regul ation of this process in disease states, antihypertensive therapy with angiotensin converting enzyme inhibitors, angiotensin II receptor ant agonists and calcium channel blockers can also modify the contribution of apoptosis, independently of the blood pressure fall. We propose th at the presence of apoptotic windows and the involvement of this biolo gical process as a primary or secondary event in cardiovascular remode ling should be taken into account when designing innovative therapeuti c approaches.