Mitochondrial H2O2 contributes to flow-mediated dilation (FMD) in human coronary arterioles (HCA). We examined the hypothesis that the endothelial cytoskeleton plays a critical role in transducing endothelial wall shear stress into a stimulus for releasing mitochondrial ROS. Phallacidin together with alpha-, beta-tubulin antibodies and Mito-Tracker Red showed the proximity of F-actin, microtubules and mitochondria in endothelial cells. Cytochalasin D (CytoD) and nocodazole (Noc) disrupted endothelial F-actin and microtubules in HCA, respectively, concurrent with a reduction in the generation of cytosolic O-2(center dot-) and H2O2 (hydroethidine and dichlorodihydrofluorescein fluorescence) and mitochondrial superoxide (mitoSox) during flow (control: 3.5 +/- 1.6, Cyto D: 0.51 +/- 0.2, Noc: 0.81 +/- 0.6). FMD, but not the dilation to bradykinin or papaverine, was reduced by Cyto D (26 +/- 10% vs. 56 +/- 3%) or Noc (26 +/- 11% vs. 58 +/- 7%). These results suggest that cytoskeletal elements are a critical component of the signaling mechanism linking endothelial shear stress and mitochondrial release of ROS in the human coronary microcirculation.
基金:
NHLBI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01 HL080704, R01 HL080704-03] Funding Source: Medline; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL080704] Funding Source: NIH RePORTER
第一作者单位:[4]NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA
通讯作者:
通讯机构:[1]Med Coll Wisconsin, Vet Adm Med Ctr, Milwaukee, WI 53226 USA[2]Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA[3]Ctr Cardiovasc, Milwaukee, WI USA[*1]Med Coll Wisconsin, Vet Adm Med Ctr, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA
推荐引用方式(GB/T 7714):
Liu Yanping,Li Hongwei,Bubolz Aaron H.,et al.Endothelial cytoskeletal elements are critical for flow-mediated dilation in human coronary arterioles[J].MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING.2008,46(5):469-478.doi:10.1007/s11517-008-0331-1.
APA:
Liu, Yanping,Li, Hongwei,Bubolz, Aaron H.,Zhang, David X.&Gutterman, David D..(2008).Endothelial cytoskeletal elements are critical for flow-mediated dilation in human coronary arterioles.MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING,46,(5)
MLA:
Liu, Yanping,et al."Endothelial cytoskeletal elements are critical for flow-mediated dilation in human coronary arterioles".MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING 46..5(2008):469-478