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Apoptosis in target organs of hypertension
1Centre de Recherche Hôtel-Dieu de Montréal, Université de Montréal, Canada.
Insights
Hypertension is linked to increased programmed cell death (apoptosis) in major organs like the heart, kidney, and brain. This study reveals cell death dysregulation as a key factor in hypertension, suggesting new therapeutic targets.
Area of Science:
- Cardiovascular Biology
- Cellular Pathology
- Hypertension Research
Background:
- Hypertension is associated with organ remodeling, including hypertrophy and hyperplasia.
- Programmed cell death (apoptosis) plays a role in cell proliferation and differentiation.
- The extent of apoptosis in hypertension-affected organs is not fully understood.
Purpose of the Study:
- To investigate the degree of apoptosis in the heart, kidney, and brain of genetically hypertensive rodents.
- To examine apoptosis in cultured vascular smooth muscle cells from hypertensive models.
- To identify potential therapeutic targets related to cell death dysregulation in hypertension.
Main Methods:
- In situ evaluation of apoptosis using morphological features, DNA fragmentation, and terminal deoxynucleotidyl transferase labeling.
- Analysis of apoptosis in whole organs (heart, kidney, brain) of spontaneously hypertensive rats and mice.
- Assessment of apoptosis in cultured aortic smooth muscle cells derived from spontaneously hypertensive rats.
Main Results:
- First evidence of increased apoptosis in the heart of spontaneously hypertensive rats.
- Increased apoptosis observed in the heart, kidney, and brain of spontaneously hypertensive mice.
- Enhanced apoptotic response to inducers in cultured aortic smooth muscle cells from spontaneously hypertensive rats.
Conclusions:
- Cell death dysregulation is significant in the pathogenesis of hypertension.
- Increased apoptosis in multiple organs highlights a novel aspect of hypertension.
- Findings suggest new avenues for therapeutic intervention in hypertension management.
Abstract:
Apoptosis or programmed cell death frequently parallels abnormalities in cell proliferation and differentiation. As hypertrophy/hyperplasia or remodeling occurs in organs affected by hypertension, we evaluated the degree of apoptosis in the heart, kidney, and brain in situ in genetically hypertensive mice and rats as well as in cultured vascular smooth muscle cells. Apoptosis was characterized by morphological features, DNA fragmentation, and laddering as well as by terminal deoxynucleotidyl transferase labeling of the 3' OH ends of both extracted DNA and tissue sections. The present report provides the first evidence of increased apoptosis in whole organs of genetically hypertensive rat and mouse strains: in the heart of spontaneously hypertensive rats (SHR) and in the heart (ventricular cardiomyocytes), kidney (inner cortex and medulla), and brain (cortex, striatum, hippocampus, and thalamus) of spontaneously hypertensive mice, with a higher effect of apoptotic inducers in cultured aortic smooth muscle cells derived from SHR. Both types of known apoptotic processes, oligonucleosomal cleavage and large DNA fragmentation, were observed in vascular smooth muscle cells, but only the former appeared to be increased in SHR. This study underlines the importance of cell death dysregulation in hypertension, reveals a new route for investigation of the pathogenesis of hypertension, and suggests novel targets of therapeutic intervention.