Chintan Gandhi

Publications (6)31.07 Total impact

• Article: ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia/reperfusion injury in mice.

  Chintan Gandhi, David G Motto, Melissa Jensen, Steven R Lentz, Anil K Chauhan
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  ABSTRACT: Epidemiological studies suggest that elevated VWF levels and reduced ADAMTS13 activity in the plasma are risk factors for myocardial infarction. It remains unknown, however, whether the ADAMTS13-VWF axis plays a causal role in the pathophysiology of myocardial infarction. We tested the hypothesis that ADAMTS13 reduces VWF-mediated acute myocardial ischemia/reperfusion (I/R) injury in mice. Infarct size, neutrophil infiltration and myocyte apoptosis in the left ventricular area was quantified after 30 minutes of ischemia and 23.5 hours of reperfusion injury. We report that Adamts13(-/-) mice exhibited significantly larger infarcts concordant with increased neutrophil infiltration and myocyte apoptosis compared with wild-type (WT) mice. In contrast, Vwf (-/-) mice exhibited significantly reduced infarct size, neutrophil infiltration, and myocyte apoptosis compared with WT mice, suggesting a detrimental role for VWF in myocardial I/R injury. Treating WT or Adamts13(-/-) mice with neutralizing antibodies to VWF significantly reduced infarct size compared with control Ig-treated mice. Finally, myocardial I/R injury in Adamts13(-/-)/Vwf (-/-) mice was similar to that in Vwf (-/-) mice, suggesting that the exacerbated myocardial I/R injury observed in the setting of ADAMTS13 deficiency is VWF-dependent. These findings reveal that ADAMTS13 and VWF are causally involved in myocardial I/R injury.
  Blood 09/2012; · 9.90 Impact Factor
• Article: Alternatively-spliced extra domain A of fibronectin promotes acute inflammation and brain injury after cerebral ischemia in mice.

  Mohammad Moshahid Khan, Chintan Gandhi, Neelam Chauhan, Jeff W Stevens, David G Motto, Steven R Lentz, Anil K Chauhan
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  ABSTRACT: The fibronectin isoform containing the alternatively spliced extra domain A (EDA(+)-FN) is normally absent from the circulation, but plasma levels of EDA(+)-FN can become markedly elevated in several human pathological conditions associated with inflammation including ischemic stroke. It remains unknown whether EDA(+)-FN contributes to stroke pathogenesis or is simply an associative marker. Several in vitro studies suggest that EDA(+)-FN can activate Toll-like receptor 4, an innate immune receptor that triggers proinflammatory responses. We undertook a genetic approach in mice to investigate the ability of EDA(+)-FN to mediate inflammatory brain damage in a focal cerebral ischemia/reperfusion injury model. We used genetically modified EDA(+/+) mice, which constitutively express EDA(+)-FN. Extent of injury, neurological outcome, and inflammatory mechanisms were assessed after 1-hour cerebral ischemia/23-hour reperfusion injury and compared with wild-type mice. We found that EDA(+/+) mice developed significantly larger infarcts and severe neurological deficits that were associated with significant increased neutrophil and macrophage infiltration as quantitated by immunohistochemistry. Additionally, we found upregulation of nuclear factor-κB, cyclo-oxygenase-2, and inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the EDA(+/+) mice compared with wild-type mice. Interestingly, increased brain injury and neurological deficits were largely abrogated in EDA(+/+) mice by treatment with a specific Toll-like receptor 4 inhibitor. These findings provide the first evidence that EDA(+)-FN promotes inflammatory brain injury after ischemic stroke and suggest that the elevated levels of plasma EDA(+)-FN observed in chronic inflammatory conditions could worsen injury and outcome in patients after acute stroke.
  Stroke 02/2012; 43(5):1376-82. · 5.73 Impact Factor
• Article: ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice.

  Chintan Gandhi, Mohammad Moshahid Khan, Steven R Lentz, Anil K Chauhan
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  ABSTRACT: ADAMTS13, a metalloprotease, plays a pivotal role in preventing spontaneous microvascular thrombosis by cleaving hyperactive ultra large von Willebrand factor multimers into smaller, less active multimers. Reduced ADAMTS13 activity in plasma has been described in many diseases associated with systemic inflammation. It remains uncertain, however, whether ADAMTS13 contributes to disease pathogenesis or rather simply serves as an inflammation-associated marker. We hypothesized that, by decreasing vascular inflammation, ADAMTS13 reduces the development of early atherosclerotic plaques. Using intravital fluorescence microscopy, we observed excessive leukocyte adhesion and accelerated atherosclerotic plaque formation at the carotid sinus of Adamts13(-/-)/ApoE(-/-) mice compared with ApoE(-/-) mice fed a high-fat Western diet. At 4 months of age, there was a significant increase in atherosclerosis in the aorta and aortic sinus of Adamts13(-/-)/ApoE(-/-) mice compared with ApoE(-/-) mice. Interestingly, we detected a 2-fold increase in macrophage recruitment to the atherosclerotic plaque of the Adamts13(-/-)/ApoE(-/-) mice compared with ApoE(-/-) mice, suggesting that the atherosclerotic lesions in these mice were not only larger but also more inflammatory. These findings reveal a new functional role for the antithrombotic enzyme ADAMTS13 in reducing excessive vascular inflammation and plaque formation during early atherosclerosis.
  Blood 11/2011; 119(10):2385-91. · 9.90 Impact Factor
• Article: Protection against in vivo focal myocardial ischemia/reperfusion injury-induced arrhythmias and apoptosis by hesperidin.

  Chintan Gandhi, Aman Upaganalawar, R Balaraman
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  ABSTRACT: Among the heart diseases, ischemia and reperfusion (I/R) induced arrhythmias contribute to episodes of sudden death. Cardiac arrhythmias during ischemia reperfusion are believed to be related to oxidative stress. Therefore, the aim of this study was to examine whether treatment with hesperidin alleviates arrhythmias and infarct size in experimentally-induced myocardial I/R injury using an in vivo rat model. In this study haemodynamics parameters, markers of inflammation, biomarkers of oxidative stress and tissue nitrite level and infarct size of the heart were estimated in various groups. I/R showed a significant decrease in tissue nitrite and antioxidant level and significant increase in arrhythmias, inflammation and myocardial cell apoptosis. Treatment with hesperidin showed a significant increase in tissue nitrite, antioxidant level and reduction in inflammation, arrhythmias and apoptosis. In conclusion, the protecting effect of hesperidin in I/R induced arrhythmias is due to reduction in inflammation and oxidative stress.
  Free radical research 08/2009; 43(9):817-27. · 2.22 Impact Factor
• Article: Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.

  Aman Upaganlawar, Chintan Gandhi, Ramchandran Balaraman
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  ABSTRACT: The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.
  Materiae Vegetabiles 01/2009; 64(1):75-80. · 2.51 Impact Factor
• Article: Nebivolol reduces experimentally induced warm renal ischemia reperfusion injury in rats.

  Chintan Gandhi, Rishit Zalawadia, R Balaraman
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  ABSTRACT: Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. The objective of the present study was to examine the role of nebivolol in modulating peroxynitrite species-induced inflammation and apoptosis after renal warm ischemia/reperfusion injury in rats. The present study was designed to investigate the effects of nebivolol on the renal warm ischemia/reperfusion injury in rats treated with the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester. After right nephrectomy, nebivolol was administered for 15 days. On the 16(th) day, ischemia was induced in contra lateral kidney for 45 min, followed by reperfusion for 24 hr. Renal function, inflammation, and apoptosis were estimated at the end of 24 hr reperfusion. Nebivolol improved the renal dysfunction and reduced inflammation and apoptosis after renal ischemia/reperfusion injury. In conclusion, nebivolol shows potent anti-apoptotic and anti-inflammatory properties due to its NO-releasing property. These findings may have major implications in the treatment of human ischemic acute renal failure.
  Renal Failure 02/2008; 30(9):921-30. · 0.82 Impact Factor