Browsing by Author "Choy, Jenny S."

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    Compensatory enlargement of Ossabaw miniature swine coronary arteries in diffuse atherosclerosis
    (Elsevier, 2015-03) Choy, Jenny S.; Luo, Tong; Huo, Yunlong; Wischgoll, Thomas; Schultz, Kyle; Teague, Shawn D.; Sturek, Michael; Kassab, Ghassan S.; Department of Biomedical Engineering, School of Engineering and Technology
    Studies in human and non-human primates have confirmed the compensatory enlargement or positive remodeling (Glagov phenomenon) of coronary vessels in the presence of focal stenosis. To our knowledge, this is the first study to document arterial enlargement in a metabolic syndrome animal model with diffuse coronary artery disease (DCAD) in the absence of severe focal stenosis. Two different groups of Ossabaw miniature pigs were fed a high fat atherogenic diet for 4 months (Group I) and 12 months (Group II), respectively. Group I (6 pigs) underwent contrast enhanced computed tomographic angiography (CCTA) and intravascular ultrasound (IVUS) at baseline and after 4 months of high fat diet, whereas Group II (7 pigs) underwent only IVUS at 12 months of high fat diet. IVUS measurements of the left anterior descending (LAD), left circumflex (LCX) and right coronary (RCA) arteries in Group I showed an average increase in their lumen cross-sectional areas (CSA) of 25.8%, 11.4%, and 43.4%, respectively, as compared to baseline. The lumen CSA values of LAD in Group II were found to be between the baseline and 4 month values in Group I. IVUS and CCTA measurements showed a similar trend and positive correlation. Fractional flow reserve (FFR) was 0.91 ± 0.07 at baseline and 0.93 ± 0.05 at 4 months with only 2.2%, 1.6% and 1% stenosis in the LAD, LCX and RCA, respectively. The relation between percent stenosis and lumen CSA shows a classical Glagov phenomenon in this animal model of DCAD.
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    Endothelial actin depolymerization mediates NADPH oxidase-superoxide production during flow reversal
    (American Physiological Society (APS), 2014-01-01) Choy, Jenny S.; Lu, Xiao; Yang, Junrong; Zhang, Zhen-Du; Kassab, Ghassan S.; Department of Biomedical Engineering, Purdue School of Engineering and Technology, IUPUI
    Slow moving blood flow and changes in flow direction, e.g., negative wall shear stress, can cause increased superoxide (O2·−) production in vascular endothelial cells. The mechanism by which shear stress increases O2·− production, however, is not well established. We tested the hypothesis that actin depolymerization, which occurs during flow reversal, mediates O2·− production in vascular endothelial cells via NADPH oxidase, and more specifically, the subunit p47phox. Using a swine model, we created complete blood flow reversal in one carotid artery, while the contralateral vessel maintained forward blood flow as control. We measured actin depolymerization, NADPH oxidase activity, and reactive oxygen species (ROS) production in the presence of various inhibitors. Flow reversal was found to induce actin depolymerization and a 3.9 ± 1.0-fold increase in ROS production as compared with forward flow. NADPH oxidase activity was 1.4 ± 0.2 times higher in vessel segments subjected to reversed blood flow when measured by a direct enzyme assay. The NADPH oxidase subunits gp91phox (Nox2) and p47phox content in the vessels remained unchanged after 4 h of flow reversal. In contrast, p47phox phosphorylation was increased in vessels with reversed flow. The response caused by reversed flow was reduced by in vivo treatment with jasplakinolide, an actin stabilizer (only a 1.7 ± 0.3-fold increase). Apocynin (an antioxidant) prevented reversed flow-induced ROS production when the animals were treated in vivo. Cytochalasin D mimicked actin depolymerization in vitro and caused a 5.2 ± 3.0-fold increase in ROS production. These findings suggest that actin filaments play an important role in negative shear stress-induced ROS production by potentiating NADPH oxidase activity, and more specifically, the p47phox subunit in vascular endothelium.