Endothelial calreticulin deletion impairs endothelial function in aged mice.

Endothelial calreticulin deletion impairs endothelial function in aged mice. Am J Physiol Heart Circ Physiol. 2020 Mar 20;: Authors: Biwer LA, Askew-Page HR, Hong K, Milstein J, Johnstone SR, Macal E, Good ME, Bagher P, Sonkusare S, Isakson BE Abstract Discrete calcium signals within the vascular endothelium decrease with age and contribute to impaired endothelial dependent vasodilation. Calreticulin (Calr), a multifunctional calcium binding protein and endoplasmic reticulum (ER) chaperone, can mediate calcium signals and vascular function within the endothelial cells (EC) of small resistance arteries. We found Calr protein expression significantly decreases with age in mesenteric arteries and examined the functional role of EC Calr in vasodilation and calcium mobilization in the context of aging. Third order mesenteric arteries from mice with or without EC Calr knockdown were examined for calcium signals and constriction to phenylephrine (PE) or vasodilation to carbachol (CCh) after 75 weeks of age. PE constriction in aged mice with or without EC Calr was unchanged. However, calcium signals and vasodilation to endothelial dependent agonist carbachol were significantly impaired in aged EC Calr knockdown mice. Ex-vivo incubation of arteries with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) significantly improved vasodilation in mice lacking EC Calr. Our data suggests diminished vascular Calr expression with age can contri...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research