Apoptosis Occurs in Endothelial Cells during Hypertension-Induced Microvascular Rarefaction

doi:10.1006/jsbi.1996.3835

Journal of Structural Biology

Volume 118, Issue 1, February 1997, Pages 63-72

https://doi.org/10.1006/jsbi.1996.3835 Get rights and content

Abstract

Disappearance of microvessels (microvascular rarefaction) during hypertension is a process that exacerbates the hypertensive condition. The cellular process by which the vessels disappear is not known. In the present study, we investigate the pathogenic role of cell death, specifically apoptosis, in hypertension-induced microvascular rarefaction. An established rodent one kidney/one clip (1K1C) Goldblatt model of hypertension was used. Histological and ultrastructural characteristics of apoptosis and necrosis were used to define incidence of the two types of cell death. The new method ofin situend-labeling DNA fragmentation known to occur in apoptosis was analyzed, and expression of an apoptosis-related gene, clusterin, identified using Northern blots andin situhybridization. Microvessels in skeletal muscle were compared in 1K1C animals (n = 3 per time point) and control animals (n = 6) at experimental times after surgery up to established hypertension (1, 2, and 4 days and 1, 2, and 6 weeks). Loss of microvessels in hypertensive animals was verified. Endothelial cell apoptosis, not necrosis, was identified and was more frequent in hypertensive animals than in controls. Apoptosis of endothelial cells was found most often within 1 week after 1K1C surgery. Clusterin mRNA transcripts were increased above control levels in all 1K1C treatments, but expression was not localized specifically above endothelial cells. In this instance, increased expression of clusterin in hypertensive animals may be an epiphenomenon, not directly related to the presence of apoptosis. The results demonstrate a role for apoptosis in the development of microvascular rarefaction in hypertension. The significance of this novel finding is that these results may now be used to direct site-specific anti-apoptosis therapy for treatment of structural rarefaction, at present unaffected by conventional anti-hypertensive therapies.

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Regular ArticleApoptosis Occurs in Endothelial Cells during Hypertension-Induced Microvascular Rarefaction

Abstract

Biochem. Biophys. Res. Commun.

Microvasc. Res.

Immunol. Today

Microvasc. Res.

Pathol. Res. Pract.

TEM

Kidney Int.

Hepatology

Methods Cell Biol.

Exp. Cell Res.

In situ end labelling detects DNA strand breaks in apoptosis and other physiological and pathological states

J. Pathol.

Mechanism of deletion of endothelial cells during regression of the corpus luteum

Lab. Invest.

Pressure-independent arteriolar rarefaction in hypertension

Am. J. Physiol.

Localization of vascular resistance changes during hypertension

Hypertension

Vascular remodelling in primary pulmonary hypertension. Potential role for transforming growth factor-β

Am. J. Pathol.

Induction of the TRPM-2 gene in cells undergoing programmed cell death

Mol. Cell. Biol.

Microvascular rarefaction in spontaneously hypertensive rat cremaster muscle

Am. J. Physiol.

Expression of clusterin in human renal diseases

Kidney Int.

Localized vascular regression during limb morphogenesis in the chicken embryo. I. Spatial and temporal changes in the vascular pattern

Anat. Rec.

Acute effects of pressure on resistance vessel geometry

Clin. Sci. Mol. Med.

Regular Article
Apoptosis Occurs in Endothelial Cells during Hypertension-Induced Microvascular Rarefaction