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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-3-26
pubmed:abstractText
PKC-beta inhibitor Ruboxistaurin (RBX or LY333531) can be used to reverse diabetic microvascular complication. However, it has not been previously established whether RBX can protect against ischemia/reperfusion (I/R) injury of cardiac microvessels in diabetic rats. STZ-induced diabetic rats were randomized into four groups and underwent I/R procedures. Cardiac barrier function and the region of cardiac microvascular lesion were examined. Cell monolayer barrier function was detected in cultured cardiac microvascular endothelial cells (CMECs) subjected to simulated I/R (SI/R). PKC-beta siRNA was transfected into CMECs to silence PKC-beta. Apoptosis Index of CMECs was detected by TUNEL assay and phosphor-LIMK2 protein expression was examined by Western blot analysis. RBX and insulin administration significantly reduced the cardiac microvascular lesion region and Apoptosis Index of endothelial cells (all P < 0.05 vs. no-treatment group). RBX decreased phosphor-LIMK2 expression (P < 0.05 vs. no-treatment group). RBX pretreatment and transfection with PKC-beta siRNA induced a rapid barrier enhancement in CMECs monolayer as detected by increased transendothelial electrical resistance (TER) and decreased FITC-dextran clearance (all P < 0.05 vs. no-treatment group). Meanwhile, RBX pretreatment and transfection with PKC-beta siRNA significantly decreased TUNEL positive CMECs and phosphor-LIMK2 expression in cultured CMECs (all P < 0.05 vs. no-treatment group). RBX pretreatment reduced F-actin/G-actin in cultured CMECs, reproducing the same effect as PKC-beta siRNA. These data indicate that PKC-beta inhibitor (RBX) may be helpful in attenuating the risk of severe cardiac microvascular I/R injury in diabetic rats partly due to its maintenance of endothelial barrier function and anti-apoptotic effect.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1573-675X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
488-98
pubmed:meshHeading
pubmed-meshheading:20044781-Actins, pubmed-meshheading:20044781-Animals, pubmed-meshheading:20044781-Apoptosis, pubmed-meshheading:20044781-Diabetes Mellitus, Experimental, pubmed-meshheading:20044781-Down-Regulation, pubmed-meshheading:20044781-Electric Impedance, pubmed-meshheading:20044781-Endothelial Cells, pubmed-meshheading:20044781-Glucose, pubmed-meshheading:20044781-Indoles, pubmed-meshheading:20044781-Lim Kinases, pubmed-meshheading:20044781-Male, pubmed-meshheading:20044781-Maleimides, pubmed-meshheading:20044781-Microvessels, pubmed-meshheading:20044781-Myocardium, pubmed-meshheading:20044781-Protective Agents, pubmed-meshheading:20044781-Protein Kinase C, pubmed-meshheading:20044781-Protein Kinase Inhibitors, pubmed-meshheading:20044781-Rats, pubmed-meshheading:20044781-Rats, Sprague-Dawley, pubmed-meshheading:20044781-Reperfusion Injury
pubmed:year
2010
pubmed:articleTitle
A PKC-beta inhibitor protects against cardiac microvascular ischemia reperfusion injury in diabetic rats.
pubmed:affiliation
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't