Apoptosis in Target Organs of Hypertension

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.

Fas Expression and Apoptosis Correlate With Cardiac Dysfunction in Patients With Dilated Cardiomyopathy

“…The contribution of apoptosis to cell death of myocytes in cardiovascular disorders such as hypertension, 17 heart failure 18 and myocytic hypoxia, 6 has recently been investigated in animal models. In a study in rats, Cheng et al showed that overstretching of a single myocyte might be related to the expression of Fas and to programmed cell death, suggesting that apoptosis may cause dilatation of the chamber.…”

Recombinant adeno-associated virus-mediated human kallikrein gene therapy protects against hypertensive target organ injuries through inhibiting cell apoptosis

“…Kinin+Hoe140 had no effects on the LPS-induced increase in caspase 3 activity. npg the heart, kidney and aorta of hypertensive patients, resulting in heart failure, renal dysfunction and vascular remodeling [11] . The present study demonstrated that a single intravenous injection of rAAV-HK could protect against apoptosis in these organs of SHRs.…”

“…Twelve three-month-old male SHRs weighing 250-280 g were randomly divided into two groups (six rats in each group). A single injection of rAAV-HK (about 1×10 11 transducing units in 1 mL of saline solution) into the tail of the SHRs was administered in the treatment group. For the control group, the SHRs were injected with rAAV-lacZ.…”

Efecto del alprostadil en los cultivos de músculo esquelético isquémico. Estudio proteómico comparativo frente a músculo sano

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