A5057730320- Atherosclerosis and Cardiovascular Diseases
- Signaling Pathways in Disease
- Bone and Dental Protein Studies
- Galectins and Cancer Biology
- Calpain Protease Function and Regulation
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Advanced Glycation End Products research
- Adipokines, Inflammation, and Metabolic Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Development and Disorders
- Pain Mechanisms and Treatments
- Retinal Diseases and Treatments
- Muscle Physiology and Disorders
- Cytomegalovirus and herpesvirus research
- Ion Channels and Receptors
- Diabetes and associated disorders
- Adenosine and Purinergic Signaling
- Phytochemicals and Antioxidant Activities
- IL-33, ST2, and ILC Pathways
- Angiogenesis and VEGF in Cancer
- Pancreatitis Pathology and Treatment
- NF-κB Signaling Pathways
- Estrogen and related hormone effects
- Glaucoma and retinal disorders
Lund University
2009-2018
Temple University
2013
Louisiana State University Health Sciences Center Shreveport
2013
Linköping University
2009
University of Virginia
2009
University of New Mexico
2009
Significance Nonsteroidal antiinflammatory drugs (NSAIDs) work by inhibiting cyclooxygenase-2 (COX-2) induced at sites of inflammation. They are among the most widely used worldwide, but their cardiovascular side effects a major concern for patients, regulators, and industry. NSAID mediated inhibition constitutively expressed COX-2 present in discrete regions, including kidney. However, pathways driving constitutive remain poorly understood. The presented here defines these importantly shows...
The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic β-cell function by potentiating insulin secretion and proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis Glucose Insulin-Related Traits Consortium [MAGIC]) showed to postprandial at the receptor (GIPR) locus. Here we explored mechanisms that could explain protective effects on islet function.Associations GIPR rs10423928 with metabolic anthropometric...
Hyperglycemia is a recognized risk factor for cardiovascular disease in diabetes. Recently, we reported that high glucose activates the Ca(2+)/calcineurin-dependent transcription nuclear of activated T cells (NFAT) arteries ex vivo. Here, sought to determine whether hyperglycemia NFAT vivo and this leads vascular complications.An intraperitoneal glucose-tolerance test mice increased NFATc3 accumulation smooth muscle. Streptozotocin-induced diabetes resulted transcriptional activity...
Interleukin-19 (IL-19) is a putative Th2, anti-inflammatory interleukin. Its expression and potential role in atherogenesis are unknown. IL-19 not detected normal artery expressed to greater degree plaque from symptomatic versus asymptomatic patients, suggesting compensatory counter-regulatory function. We tested whether could reduce atherosclerosis susceptible mice identified plausible mechanisms.LDLR(-/-) fed an atherogenic diet injected with either 1.0 or 10.0 ng/g per day recombinant...
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected of GIP signaling in the vasculature. induces expression proatherogenic cytokine osteopontin (OPN) mouse arteries via local release endothelin-1 and activation CREB. Infusion increases plasma OPN concentrations healthy individuals. Plasma are positively correlated patients critical limb ischemia. Fasting higher individuals a history...
Objective of the Study Diabetic patients have a much more widespread and aggressive form atherosclerosis therefore, higher risk for myocardial infarction, peripheral vascular disease stroke, but molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates transcription factor NFAT in arterial wall, inducing expression pro-atherosclerotic protein osteopontin. Here investigate whether activation may be link between diabetes...
Alternative transcription and splicing of the allograft inflammatory factor-1 (AIF-1) gene results in expression two different proteins: AIF-1 interferon responsive transcript-1 (IRT-1). Here, we explore impact IRT-1 on vascular smooth muscle cell (VSMC) activation neointima formation, mechanisms underlying their alternative splicing, associations mRNA with parameters defining human atherosclerotic plaque phenotype.Translation products contrasting cellular distribution functions....
Aims Sight-threatening diabetic retinopathy has been treated with photocoagulation for decades but the mechanisms behind beneficial clinical effects are poorly understood. One target of irradiation and a potential player in this process is retinal pigment epithelium (RPE). Here we establish an vitro model human RPE cells. Methods ARPE-19 cells were exposed to studied at various time points up 168h. Lesion morphology, necrosis apoptosis investigated by light microscopy; LIVE/DEAD staining...
The pathogenesis of diabetic retinopathy (DR) remains unclear but hyperglycemia is an established risk factor. Endothelial dysfunction and changes in Ca 2+ signaling have been shown to precede the onset DR. We recently demonstrated that high extracellular glucose activates /calcineurin-dependent transcription factor NFAT cerebral arteries aorta, promoting expression inflammatory markers. Here we show, using confocal immunofluorescence, expressed endothelium retinal microvessels readily...
Vascular inflammation is a key feature of both micro- and macrovascular complications in diabetes. Several lines evidence have implicated the cytokine tumor necrosis factor (TNF) alpha as an important mediator In present study we evaluated role TNF streptozotocin (STZ)-induced diabetes on vascular C57BL/6 wild-type apoE-/- mice.Diabetes increased expression cell adhesion molecule (VCAM)-1 cerebral arteries 150 m diameter well macrophage accumulation aortic root atherosclerotic plaques mice....
Aims: Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here, we investigated effects of nuclear factor activated T-cells inhibition on plaque burden in a novel mouse model type 2 that better replicates human disease. Methods & Results: IGF-II/LDLR –/– ApoB 100/100 mice were generated by crossbreeding low-density lipoprotein receptor–deficient synthesize only apolipoprotein B100 (LDLR...
Hyperglycemia is a recognized risk factor for cardiovascular disease in diabetes. Recently we reported that high glucose activates the transcription NFAT arteries ex vivo . Here, investigate if hyperglycemia and whether this leads to vascular complications. Intra peritoneal tolerance test mice increased NFATc3 nuclear accumulation smooth muscle. Streptozotocin‐induced diabetes augmented transcriptional activity of NFAT‐luciferase transgenic mice. Two responsive sequences were identified...
Diabetes is associated with devastating macrovascular complications including coronary heart disease and stroke. The molecular mechanisms leading to vascular are still poorly understood. We have previously shown that hyperglycemia activates the transcription factor NFAT in native arteries. Once activated, promotes cell proliferation, enhances SMC excitability expression of inflammatory markers (i.e. IL‐6, tissue factor, COX‐2). Here we tested whether involved development disease. Treatment...
Hyperglycemia is an important risk factor for the development of diabetic retinopathy. Recently we showed that high glucose activates NFAT in cerebral artery smooth muscle through local release extracellular nucleotides, acting on P2Y receptors, leading to increased [Ca 2+ ] i and calcineurin activation. activation promotes cell proliferation expression inflammatory markers, such as IL‐6, COX‐2 osteopontin, which are elevated Here investigate whether: 1) activated by hyperglycemia wall...