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The time window of apoptosis: a new component in the therapeutic strategy for cardiovascular remodeling
1Centre de Recherche Hôtel-Dieu de Montréal, Université de Montreal, Quebec, Canada.
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.
Insights
Apoptosis, or programmed cell death, is altered in hypertension, with reduced early apoptosis and increased later apoptosis. Antihypertensive drugs may also modify apoptosis, impacting cardiovascular remodeling.
Area of Science:
- Cardiovascular Biology
- Cell Death Mechanisms
- Hypertension Research
Background:
- Apoptosis (programmed cell death) is a critical cellular process.
- Hypertension is associated with changes in cell replication and death.
- Previous studies indicated increased apoptosis in hypertensive organs.
Purpose of the Study:
- To investigate the role and regulation of apoptosis in hypertension.
- To examine the temporal dynamics of apoptosis during hypertension development.
- To assess the impact of antihypertensive therapy on apoptosis.
Main Methods:
- Studies in spontaneously hypertensive rats (SHR) and mice.
- Analysis of apoptosis in heart, kidney, and brain tissues.
- Investigation of cultured vascular smooth muscle cells.
- Evaluation of experimental cardiac hypertrophy models.
- Assessment of antihypertensive treatments (ACE inhibitors, ARBs, CCBs).
Main Results:
- Apoptosis is reduced early in SHR life, potentially contributing to hyperplasia.
- Increased apoptosis is observed during hypertension development.
- Apoptosis levels decrease in SHR after 24 weeks.
- Antihypertensive therapies can modulate apoptosis independently of blood pressure reduction.
Conclusions:
- Hypertension involves dynamic, prolonged "apoptotic windows."
- Apoptosis plays a significant role in cardiovascular remodeling in hypertension.
- Therapeutic strategies should consider the role of apoptosis in cardiovascular disease.