title: The time window of apoptosis: a new component in the therapeutic strategy for cardiovascular remodeling.
abstract: APOPTOSIS AND EXPERIMENTAL HYPERTROPHY: Apoptosis (programmed cell death) is a physiological counterpart of cell replication with shared as well as specific pathways. Our initial studies have demonstrated increased apoptosis in the heart, kidney and brain of spontaneously hypertensive rats (SHR) and mice, persisting in cultured vascular smooth muscle cells. In these target organs of hypertension, programmed cell death paralleled the well known hypertrophy/hyperplasia. We also observed that the two processes can be dissociated in time, as in experimental hypertrophy 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 more prolonged apoptotic window is present in hypertension. Apoptosis seems to be significantly reduced during the first weeks of life in SHR, possibly contributing to the early cardiac hyperplasia. However, increased apoptosis is clearly evident thereafter throughout the development of hypertension and fades below the levels observed in normotensive animals after the age of 24 weeks. ANTIHYPERTENSIVE THERAPY AND APOPTOSIS: In addition to the apoptotic windows that suggest a dynamic regulation of this process in disease states, antihypertensive therapy with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium channel blockers can also modify the contribution of apoptosis, independently of the blood pressure fall. We propose that the presence of apoptotic windows and the involvement of this biological process as a primary or secondary event in cardiovascular remodeling should be taken into account when designing innovative therapeutic approaches.
authors.affiliation: Centre de Recherche Hôtel-Dieu de Montréal, Université de Montreal, Quebec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Hamet
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.forename: T V
authors.initials: TV
authors.lastname: Dam
authors.forename: S N
authors.initials: SN
authors.lastname: Orlov
authors.forename: B S
authors.initials: BS
authors.lastname: Tea
authors.forename: D
authors.initials: D
authors.lastname: de Blois
authors.forename: J
authors.initials: J
authors.lastname: Tremblay
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology / Q000517:prevention & control*; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents