A5049710084- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- PARP inhibition in cancer therapy
- Reproductive System and Pregnancy
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Cardiac Ischemia and Reperfusion
- Renal Diseases and Glomerulopathies
- Neonatal Respiratory Health Research
- Maternal and fetal healthcare
- Acute Myocardial Infarction Research
- Respiratory viral infections research
- Cell death mechanisms and regulation
- Adipose Tissue and Metabolism
- Organ Transplantation Techniques and Outcomes
- Integrated Circuits and Semiconductor Failure Analysis
- Liver Disease and Transplantation
- Hormonal Regulation and Hypertension
- Gestational Diabetes Research and Management
- Childhood Cancer Survivors' Quality of Life
- Adenosine and Purinergic Signaling
- Prenatal Screening and Diagnostics
- Virus-based gene therapy research
- Autophagy in Disease and Therapy
- Chemotherapy-induced organ toxicity mitigation
Beth Israel Deaconess Medical Center
2016-2025
Harvard University
2014-2025
Hadassah Medical Center
2014-2025
Beth Israel Deaconess Hospital
2023
Lahey Medical Center
2023
Center for Vascular Biology Research
2012-2020
American Journal Experts (United States)
2018
Boston University
2017
Radikal Therapeutics
2017
Boston Children's Museum
2016
In this report, we show that hyperglycemia-induced overproduction of superoxide by the mitochondrial electron transport chain activates three major pathways hyperglycemic damage found in aortic endothelial cells inhibiting GAPDH activity. bovine cells, antisense oligonucleotides activated each vascular cultured 5 mM glucose to same extent as induced culturing 30 glucose. Hyperglycemia-induced inhibition was be a consequence poly(ADP-ribosyl)ation poly(ADP-ribose) polymerase (PARP), which DNA...
Sepsis-associated acute kidney injury (AKI) is a common and morbid condition that distinguishable from typical ischemic renal by its paucity of tubular cell death. The mechanisms underlying dysfunction in individuals with sepsis-associated AKI are therefore less clear. Here we have shown endotoxemia reduces oxygen delivery to the kidney, without changing tissue levels, suggesting reduced consumption cells. Tubular mitochondria were swollen, their function was impaired. Expression profiling...
C5a anaphylatoxin, a potent inflammatory mediator, is known to act through specific G protein coupled receptor. However, some of the complex effects in vivo may not be explained solely by deletion Here, we show that an orphan receptor, identified as C5L2, high affinity binding protein. Unlike previously described C5aR, C5L2 obligately uncoupled from heterotrimeric proteins, part virtue amino acid alteration so-called DRY sequence at end third transmembrane segement. Both human and murine...
In this report, we show that hyperglycemia-induced overproduction of superoxide by the mitochondrial electron transport chain activates three major pathways hyperglycemic damage found in aortic endothelial cells inhibiting GAPDH activity. bovine cells, antisense oligonucleotides activated each vascular cultured 5 mM glucose to same extent as induced culturing 30 glucose. Hyperglycemia-induced inhibition was be a consequence poly(ADP-ribosyl)ation poly(ADP-ribose) polymerase (PARP), which DNA...
Sepsis is associated with increased production of superoxide and nitric oxide, consequent peroxynitrite generation. Cardiodepression induced in the heart during oxidative stress septic shock. Oxidative nitrosative can lead to activation nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase (PARP), subsequent loss myocardial contractile function. The aim study was investigate whether cardiodepression found patients plasma markers necrosis PARP activation.Prospective...
The cardinal manifestations of the pregnancy-specific disorder preeclampsia, new-onset hypertension, and proteinuria that resolve with placental delivery have been linked to an extracellular protein made by placenta, soluble fms-like tyrosine kinase 1 (sFlt1), injures maternal vasculature. However, mechanisms which sFlt1, is heavily matrix bound, gain access systemic circulation remain unclear. Here we report preeclamptic placenta's outermost layer, syncytiotrophoblast, forms abundant...
This study evaluated the effects of aldose reductase inhibition on diabetes-induced oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation. In animal experiments, control streptozotocin-induced diabetic rats were treated with or without inhibitor (ARI) fidarestat (16 mg . kg(-1) day(-1)) for 6 weeks starting from induction diabetes. Sorbitol pathway intermediate, but not glucose, accumulation in sciatic nerve retina was completely prevented fidarestat. Sciatic motor...
Preeclampsia is a hypertensive disorder of pregnancy in which patients develop profound sensitivity to vasopressors, such as angiotensin II, and associated with substantial morbidity for the mother fetus. Enhanced vasoconstrictor elevations soluble fms-like tyrosine kinase 1 (sFLT1), circulating antiangiogenic protein, precede clinical signs symptoms preeclampsia. Here, we report that overexpression sFlt1 pregnant mice induced II hypertension by impairing endothelial nitric oxide synthase...
Cisplatin is a widely used antineoplastic agent. However, its major limitation dose-dependent nephrotoxicity whose precise mechanism poorly understood. Recent studies have suggested that mitochondrial dysfunction in tubular epithelium contributes to cisplatin-induced nephrotoxicity. Here the authors extend those findings by describing role of an important electron transport chain enzyme, cytochrome c oxidase (COX). Immunohistochemistry for COX 1 protein demonstrated that, response cisplatin,...
Soluble fms-like tyrosine kinase 1 (sFlt1), a circulating antiangiogenic protein, is elevated in kidney diseases and contributes to the development of preeclampsia. Hydrogen sulfide vasorelaxant proangiogenic gas with therapeutic potential several diseases. Therefore, we evaluated effect mechanisms action hydrogen an animal model sFlt1-induced hypertension, proteinuria, glomerular endotheliosis created by adenovirus-mediated overexpression sFlt1 Sprague-Dawley rats. We injected...
The transcriptional coactivators PGC-1α and PGC-1β are widely thought to be required for mitochondrial biogenesis fiber typing in skeletal muscle. Here, we show that mice lacking both PGC-1s myocytes do indeed have profoundly deficient respiration but, surprisingly, preserved content, isolated muscle contraction capacity, fiber-type composition, in-cage ambulation, voluntary running capacity. Most of these findings recapitulated cell culture and, thus, autonomous. Functional electron...
To evaluate the role of cell-mediated immunity during gene transfer to respiratory epithelium, time course luciferase activity was assessed after intratracheal administration Av1Luc1, an E1a-E3-deleted adenoviral (Ad5) vector expressing firefly luciferase, FVB/N, BALB/c and BALB/c-nu/nu adult mice. Adenovirus-mediated rapidly lost from tract between 2 14 days treatment both FVB/N wild-type In mice, loss associated with early inflammatory response consisting infiltration macrophages...
ABSTRACT Adenovirus is a common respiratory pathogen which causes broad range of distinct clinical syndromes and has recently received attention for its potential in vivo gene delivery. Although adenovirus tract infection (ARTI) results dose-dependent, local inflammation, the pathogenesis this remains unclear. We hypothesized that alveolar macrophages (AMφ) rapidly internalize following pulmonary administration then initiate inflammatory signaling within lung. To evaluate role AMφ induction...
Nitrosative stress, that is, enhanced peroxynitrite formation, has been documented in both experimental and clinical diabetic neuropathy (DN), but its pathogenetic role remains unexplored.This study evaluated the for nitrosative stress two animal models of type 1 diabetes: streptozotocin-diabetic mice NOD mice.Control (C) streptozotocindiabetic (D) were treated with without potent decomposition catalyst FP15 (5 mg kg -1 d ) wk after 8 treatment.Sciatic nerve nitrotyrosine (a marker...
Placental activation of the renin-angiotensin system (RAS) plays a key role in pathogenesis preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examined ROS by genetically modifying Keap1-Nrf2 pathway, cellular antioxidant defense system, mouse model RAS-induced Nrf2 deficiency would be expected impair responses; however, preeclamptic mice improved maternal and fetal survival, ameliorated...
ABSTRACT People of recent sub-Saharan African ancestry develop kidney failure much more frequently than other groups. A large fraction this disparity is due to two coding sequence variants in the APOL1 gene. Inheriting copies these risk variants, known as G1 and G2, causes high rates focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy hypertension-associated end-stage disease. Disease follows a recessive mode inheritance, which puzzling given considerable data that G2 are...
Preeclampsia is a syndrome of high blood pressure (BP) with end organ damage in late pregnancy that associated circulating soluble VEGF receptor (sFlt1 [soluble Fms-like tyrosine kinase 1]). Women exposed to preeclampsia have substantially increased risk hypertension after pregnancy, but the mechanism remains unknown, leaving missed interventional opportunity. After preeclampsia, women enhanced sensitivity hypertensive stress. Since smooth muscle cell mineralocorticoid receptors (SMC-MR) are...
The human surfactant protein (SP)-C gene promoter was used to direct expression of mouse granulocyte macrophage colony-stimulating factor (GM-CSF; SP-C-GM mice) in lung epithelial cells GM-CSF-replete (GM+/+) or GM-CSF null mutant (GM−/−) mice. Lung weight and volume were significantly increased mice compared with GM+/+ GM−/− control Immunohistochemical staining demonstrated marked type II cell hyperplasia, immunofluorescent labeling for proliferating nuclear antigen Abundance per three-...