Open AccessCardiac and hepatic role of r‐At HSP 70: basal effects and protection against ischemic and sepsis conditions
Author(s) -
Pasqua Teresa,
Filice Elisabetta,
Mazza Rosa,
Quintieri Anna Maria,
Carmela Cerra Maria,
Iannacone Rina,
Melfi Donato,
Indiveri Cesare,
Gattuso Alfonsina,
Angelone Tommaso
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12491
Subject(s) - cardioprotection , sepsis , heat shock protein , nitric oxide synthase , cardiac function curve , biology , hsp70 , pharmacology , lipopolysaccharide , inotrope , proinflammatory cytokine , nitric oxide , in vivo , tumor necrosis factor alpha , reperfusion injury , ex vivo , inflammation , immunology , ischemia , medicine , endocrinology , heart failure , biochemistry , microbiology and biotechnology , gene
Heat shock proteins ( HSP s), highly conserved in all organisms, act as molecular chaperones activated by several stresses. The HSP 70 class of stress‐induced proteins is the most studied subtype in cardiovascular and inflammatory disease. Because of the high similarity between plant and mammalian HSP 70, the aim of this work was to evaluate whether recombinant HSP 70 of plant origin (r‐At HSP 70) was able to protect rat cardiac and hepatic function under ischemic and sepsis conditions. We demonstrated for the first time that, in ex vivo isolated and perfused rat heart, exogenous r‐At HSP 70 exerted direct negative inotropic and lusitropic effects via Akt/endothelial nitric oxide synthase pathway, induced post‐conditioning cardioprotection via Reperfusion Injury Salvage Kinase and Survivor Activating Factor Enhancement pathways, and did not cause hepatic damage. In vivo administration of r‐At HSP 70 protected both heart and liver against lipopolysaccharide‐dependent sepsis, as revealed by the reduced plasma levels of interleukin‐1β, tumour necrosis factor alpha, aspartate aminotransferase and alanine aminotransferase. These results suggest exogenous r‐At HSP 70 as a molecular modulator able to protect myocardial function and to prevent cardiac and liver dysfunctions during inflammatory conditions.