Vascular Endothelial Growth Factor Upregulates Inducible Nitric Oxide Synthase Expression in the Muscle Flap Ischemia Model in the Rat

Abstract

The purpose of this investigation was to elucidate the regulation of inducible nitric oxide synthase (iNOS) expression by vascular endothelial growth factor (VEGF) in a muscle flap ischemia model in rats. The gracilis muscle flap model was chosen. Sixty adult male Sprague Dawley rats were randomly divided into two groups (n = 30). After 4 hours ischemia, the experimental group received VEGF treatment, and the control group was given saline in the same fashion. At time intervals of 0, 2, 6, 12, and 18 hours (n = 6 for each time interval) after injection, tissue samples were biopsied for reverse transcriptase polymerase chain reaction, routine hematoxylin-eosin staining, and CD31 immunohistochemical staining. The result showed that iNOS expression is increased in the gracilis muscle flap ischemia model in rats compared with the control group within 6 hours after ischemia (p < 0.05). In the VEGF group, iNOS expression increased rapidly over the first 2 hours, but no statistically significant difference was observed at 12 and 18 hours between the two groups (p > 0.05). We concluded that the application of VEGF could maintain the structure of capillaries and upregulate iNOS expression during the first 6 hours after ischemia in the ischemic muscle flap of a rat model. These findings may provide the evidence to study the mechanism of VEGF in improving flap survival.

Role of the NO/cGMP Pathway in Postoperative Vasodilation in Perforator Flaps

“…The vasodilation of NO produced by inducible nitric oxide synthase (iNOS) may be the major effect of VEGF on improving the survival of the muscle flap with a short critical ischemic time. 17 NO has been shown to be of importance during ischemia. NO, synthesized by constitutive Ca 2þ dependent NOS in the endothelium (eNOS) and perivascular nerves(nNOS), has been suggested to be tissue protective as it maintains blood flow and inhibits platelet aggregation and adhesion of leukocytes.…”

Expression of HIF-1α in Ischemia and Reperfusion in Human Microsurgical Free Muscle Tissue Transfer

“…Currently, the knowledge of these processes is very limited or findings are often based on animal models only. [12][13][14][15] Our previously published work on molecular and cellular aspects in free human muscle tissue transfer identified interesting and important changes in the regulation of gene expression; however, we did not discuss the important role of hypoxia-inducible factor (HIF)-1␣. 16 HIF-1␣ is considered one of the key enzymes in regulating gene expression after ischemia (Fig.…”

Mass spectrometric characterization of limited proteolysis activity in human plasma samples under mild acidic conditions

“…Also blood glucose measurements were suggested for flap monitoring and for establishing a simple method that can be widely applied [6,47]. Commonly, only the clinical examination of the transplanted tissue is assessed for gaining information about the status of the transplant [48][49][50][51][52]. To open an avenue towards molecular monitoring of transplants, the aim of our study was to generate a mass spectrometry-based method that is suitable to monitor plasma protease activity dynamics because such enzymatic activities can mirror pathophysiological conditions in tissues.…”