Novel cardiolipin therapeutic protects endothelial mitochondria during renal ischemia and mitigates microvascular rarefaction, inflammation and fibrosis.

NOVEL CARDIOLIPIN THERAPEUTIC PROTECTS ENDOTHELIAL MITOCHONDRIA DURING RENAL ISCHEMIA AND MITIGATES MICROVASCULAR RAREFACTION, INFLAMMATION AND FIBROSIS.
Am J Physiol Renal Physiol. 2014 Feb 19;
Authors: Liu S, Soong Y, Seshan SV, Szeto HH
Abstract
Microvascular rarefaction, or loss of microvascular density, is increasingly implicated in the progression from acute ischemic kidney injury to chronic kidney disease. Microvascular dropout results in chronic tissue hypoxia, interstitial inflammation and fibrosis. There is currently no therapeutic intervention for microvascular rarefaction. We hypothesize that capillary dropout begins with ischemic damage to endothelial mitochondria due to cardiolipin peroxidation, resulting in loss of cristae and the failure to regenerate ATP upon reperfusion. SS-31 is a cell-permeable peptide that targets the inner mitochondrial membrane and binds selectively to cardiolipin. It was recently shown to inhibit cardiolipin peroxidation by cytochrome c peroxidase activity, and it has been shown to protect mitochondrial cristae in proximal tubular cells during ischemia, and accelerated ATP recovery upon reperfusion. We found mitochondrial swelling and loss of cristae membranes in endothelial and medullary tubular epithelial cells after 45 minutes ischemia in the rat. The loss of cristae membranes limited the ability of these cells to regenerate ATP upon reperfusion and led to loss of vascular integrity and tubular cell ...

Source: Am J Physiol Renal P... - February 19, 2014 Category: Urology & Nephrology Authors: Liu S, Soong Y, Seshan SV, Szeto HH Tags: Am J Physiol Renal Physiol Source Type: research