Ischemia/reperfusion injury of the kidney is associated with high morbidity and mortality, and treatment of this injury remains a challenge. G protein-coupled receptor kinase 4 (GRK4) plays a vital role in essential hypertension and myocardial infarction, but its function in kidney ischemia/reperfusion injury remains undetermined. Among the GRK subtypes (GRK2-6) expressed in kidneys, the increase in GRK4 expression was much more apparent than that of the other four GRKs 24 hours after injury and was found to accumulate in the nuclei of injured mouse and human renal tubule cells.
View Article and Find Full Text PDFAcute myocardial infarction (MI) is one of the leading causes of death in humans. Our previous studies showed that gastrin alleviated acute myocardial ischaemia-reperfusion injury. We hypothesize that gastrin might protect against heart injury after MI by promoting angiogenesis.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
March 2018
We tested the hypothesis that hypoxia-reoxygenation (H/R) augments vasoreactivity to angiotensin II (ANG II). In particular, we compared an in situ live kidney slice model with isolated afferent arterioles (C57Bl6 mice) to assess the impact of tubules on microvessel response. Hematoxylin and eosin staining was used to estimate slice viability.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
October 2017
The incretin hormone, glucagon-like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption.
View Article and Find Full Text PDFChronic kidney disease (CKD) is a significant health problem associated with high morbidity and mortality. Despite significant research into various pathways involved in the pathophysiology of CKD, the therapeutic options are limited in diabetes and hypertension induced CKD to blood pressure control, hyperglycemia management (in diabetic nephropathy) and reduction of proteinuria, mainly with renin-angiotensin blockade therapy. Recently, renal oxygenation in pathophysiology of CKD progression has received a lot of interest.
View Article and Find Full Text PDFAcute kidney injury (AKI) continues to be a major therapeutic challenge. Despite significant advances made in cellular and molecular pathophysiology of AKI, major gaps in knowledge exist regarding the changes in renal hemodynamics and oxygenation in the early stages and through the continuum of AKI. Particular features of renal hemodynamics and oxygenation increase the susceptibility of the kidney to sustain injury due to oxygen demand-supply mismatch and also play an important role in the recovery and repair from AKI as well as the transition of AKI to chronic kidney disease.
View Article and Find Full Text PDFCurrent heart valve prostheses are associated with significant complications, including aggressive immune response, limited valve life expectancy, and inability to grow in juvenile patients. Animal derived "tissue" valves undergo glutaraldehyde fixation to mask tissue antigenicity; however, chronic immunological responses and associated calcification still commonly occur. A heart valve formed from an unfixed bovine pericardium (BP) extracellular matrix (ECM) scaffold, in which antigenic burden has been eliminated or significantly reduced, has potential to overcome deficiencies of current bioprostheses.
View Article and Find Full Text PDFNumerous studies have focused on generation of unfixed bovine pericardium (BP) extracellular matrix (ECM) for clinical application. However, the extent to which maintenance of native ECM niche is capable of directing behavior of repopulating cells remains relatively unexplored. By exploiting the sidedness of BP scaffolds (i.
View Article and Find Full Text PDFNeuregulin-1 (NRG-1) is an endothelium-derived growth factor with cardioprotective and antiatherosclerotic properties and is currently being tested in clinical trials as a treatment for systolic heart failure. In clinical practice, heart failure often coexists with renal failure, sharing an overlapping pathophysiological background. In this study, we hypothesized that NRG-1 might protect against cardiomyopathy, atherosclerosis, and nephropathy within one disease process.
View Article and Find Full Text PDFDuring the last 30 years, artificial oxygen carriers have been investigated intensively with the aim to develop universal blood substitutes. Favorably, hemoglobin-based oxygen carriers (HBOCs) are expected to meet the sophisticated requirements. However, the HBOCs tested until now show serious side effects, which resulted in failure of clinical trials and Food and Drug Administration disapproval.
View Article and Find Full Text PDFIodinated contrast media (CM) have adverse effects that may result in contrast-induced acute kidney injury. Oxidative stress is believed to play a role in CM-induced kidney injury. We test the hypothesis that oxidative stress and reduced nitric oxide in tubules are consequences of CM-induced direct cell damage and that increased local oxidative stress may increase tubuloglomerular feedback.
View Article and Find Full Text PDFArtificial oxygen carriers, favorably hemoglobin-based oxygen carriers (HBOCs), are being investigated intensively during the last 30 years with the aim to develop a universal blood substitute. However, serious side effects mainly caused by vasoconstriction triggered by nitric oxide (NO) scavenging due to penetration of nanosized HBOCs through the endothelial gaps of the capillary walls and/or oxygen oversupply in the precapillary arterioles due to their low oxygen affinity led to failure of clinical trials and FDA disapproval. To avoid these effects, HBOCs with a size between 100 and 1000 nm and high oxygen affinity are needed.
View Article and Find Full Text PDFContrast-induced acute kidney injury is an important clinical event with a worldwide increasing number of cases. Medullary hypoperfusion and hypoxia due to constriction of vasa recta are main factors in the pathophysiology of acute kidney injury. However, the mechanism of contrast media (CM)-induced vessel constriction is not known.
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