A PKC-beta inhibitor treatment reverses cardiac microvascular barrier dysfunction in diabetic rats.
The PKC-beta inhibitor ruboxistaurin (RBX or LY333531) prevents diabetic renal and retinal microvascular complications. However, the effect of RBX on diabetic cardiac microvascular dysfunction is still unclear. In this study, we aimed to investigate the effects and mechanisms of RBX treatment upon cardiac endothelial barrier dysfunction in high glucose states. We demonstrated RBX treatment suppressed high glucose induced PKC-betaII activation and phosphorylation of beta-catenin in vivo and in vitro experiments. Meanwhile, RBX treatment protected cardiac microvascular barrier function in diabetic animals and monolayer barrier function of cultured cardiac microvascular endothelial cells (CMECs), reproducing the same effect as PKC-betaII siRNA. These results provide new insight into protective properties of PKC-beta inhibitor against cardiac endothelial barrier dysfunction. PKC-beta inhibitor RBX prevented chronic cardiac microvascular barrier dysfunction and improved endothelial cell-cell junctional function in high glucose states.
Wei
Liping
L
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Yin
Zhiyong
Z
Yuan
Yuan
Y
Hwang
Andrew
A
Lee
Andrew
A
Sun
Dongdong
D
Li
Fei
F
Di
Chunxia
C
Zhang
Rongqing
R
Cao
Feng
F
Wang
Haichang
H
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006331:Heart Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007365:Intercellular Junctions / Q000187:drug effects / Q000473:pathology; D007811:Lanthanum / Q000378:metabolism; D008297:Male; D008301:Maleimides / Q000494:pharmacology / Q000627:therapeutic use; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010477:Perfusion; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051176:beta Catenin / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D005947:Glucose; D007211:Indoles; D007811:Lanthanum; D008301:Maleimides; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D051176:beta Catenin; D000099152:Cadherin 5; C495268:Ctnnb1 protein, rat; C016534:lanthanide nitrate; C099154:ruboxistaurin