Background: Currently, no therapies exist for treating and improving outcomes in patients with severe peripheral artery disease (PAD). MicroRNA93 (miR93) has been shown to favorably modulate angiogenesis reduce tissue loss genetic PAD models. However, the cell-specific function, downstream mechanisms, or signaling involved miR93-mediated ischemic muscle neovascularization is not clear. Macrophages were best known arteriogenic response PAD, extent of induced by macrophages dependent on...

Background: Atherosclerotic occlusions decrease blood flow to the lower limbs, causing ischemia and tissue loss in patients with peripheral artery disease (PAD). No effective medical therapies are currently available induce angiogenesis promote perfusion recovery severe PAD. Clinical trials aimed at inducing vascular endothelial growth factor (VEGF)–A levels, a potent proangiogenic angiogenesis, were not successful. Alternate splicing exon-8 of VEGF-A results formation VEGFxxxa (VEGF 165 a)...

Lymphatics perform essential transport and immune regulatory functions to maintain homeostasis in the gastrointestinal (GI) system. Although blood lymphatic vessels function as parallel integrated systems, our understanding of structure, regulation functioning lags far behind that vascular This chapter reviews flow, differences lymphangiogenic hemangiogenic factors, fate determinants structural features, examines how altered molecular signaling influences organs GI Innate errors development...

Atherosclerotic-arterial occlusions decrease tissue perfusion causing ischemia to lower limbs in patients with peripheral arterial disease (PAD). Ischemia muscle induces an angiogenic response, but the magnitude of this response is frequently inadequate meet requirements. Alternate splicing exon-8 vascular endothelial growth factor (VEGF)-A results production proangiogenic VEGFxxxa isoforms (VEGF165a, 165 for amino acid product) and antiangiogenic VEGFxxxb (VEGF165b) isoforms.The are thought...

BackgroundThe pathophysiology of inflammatory bowel disease (IBD) includes leukocyte infiltration, blood and lymphatic remodeling, weight loss protein enteropathy. The roles angiopoietin-2 (Ang-2) in initiating gut inflammation, infiltration angiogenesis are not well understood.

Our current study builds on our recent report that showed Palmitate aggravates ischemic endothelial (EC) dysfunction in vitro and aims to determine whether is a critical determinant of PAD severity. In contrast Palmitate, we studied the role short-chain fatty acids (SCFAs) regulating revascularization PAD. Femoral artery ligation resection was used as preclinical-PAD model. Hypoxia serum starvation dramatically decreased ischemic-EC survival angiogenic capacity , whereas SCFAs significantly...

Despite being in an oxygen-rich environment, endothelial cells (ECs) use anaerobic glycolysis (Warburg effect) as the primary metabolic pathway for cellular energy needs. PFKFB (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase)-3 regulates a critical enzymatic checkpoint and has been shown to induce angiogenesis. This study builds on our efforts determine regulation of ischemic angiogenesis perfusion recovery muscle.

Multiple sclerosis (MS) is believed to be an immune-mediated neurodegenerative disorder of the human central nervous system which usually affects younger adults with certain genetic backgrounds. The causes and cure for MS remain elusive. Based on recent advances in our understanding pathogenic mechanisms MS, it appears represents a heterogeneous group disorders dissimilar pathophysiology neuropathology. Currently, there no unifying hypothesis explain pathogenesis this complex disease. three...

Nitric oxide (NO) is the critical regulator of VEGFR2-induced angiogenesis. Neither VEGF-A over-expression nor L-Arginine (NO-precursor) supplementation has been effective in helping patients with Peripheral Artery Disease (PAD) clinical trials. One incompletely studied reason may be due to presence less characterized anti-angiogenic (VEGF165b) isoform. We have recently shown that VEGF165b inhibits ischemic angiogenesis by blocking VEGFR1, not VEGFR2 activation. Here we wanted determine...

Background In endothelial cells (ECs), glycolysis, regulated by PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, isoform-3), is the major metabolic pathway for ATP generation. preclinical peripheral artery disease models, VEGF

Traumatic brain injury (TBI) and sub-arachnoid hemorrhage (SAH) are major causes of long-term disability, mortality, enormous economic costs to society. The full spectrum neurological damage created by TBI or SAH is not usually manifested at the time injury, but evolves gradually over course hours days (or weeks) following these injuries. Angiopoietins, important regulators vascular structure function, hallmark indicators may therefore represent promising targets in treatment TBI. In animal...

Abstract Background VEGF 165 a increases the expression of microRNA-17-92 cluster, promoting developmental, retinal, and tumor angiogenesis. We have previously shown that b, an alternatively spliced anti-angiogenic VEGF-A isoform, inhibits VEGFR-STAT3 pathway in ischemic endothelial cells (ECs) to decrease their angiogenic capacity. In macrophages (Møs), b VEGFR1 induce S100A8/A9 expression, which drives M1-like polarization. Our current study aims determine whether inhibition promotes...

Alternative splicing in the eighth exon C-terminus of VEGF-A (vascular endothelial growth factor-A) results formation proangiogenic VEGF

Angiogenesis is the growth of new blood vessels from pre-existing microvessels. Peripheral arterial disease (PAD) caused by atherosclerosis that results in ischemia mostly lower extremities. Clinical trials including VEGF-A administration for therapeutic angiogenesis have not been successful. The existence anti-angiogenic isoform (VEGF165b) PAD muscle tissues a potential cause failure angiogenesis. Experimental measurements show human biopsies VEGF165b at least as abundant if greater than...

The interleukin-21 receptor (IL-21R) can be upregulated in endothelial cells (EC) from ischemic muscles mice following hind-limb ischemia (HLI), an experimental peripheral arterial disease (PAD) model, blocking this ligand–receptor pathway-impaired STAT3 activation, angiogenesis, and perfusion recovery. We sought to identify mRNA microRNA transcripts that were differentially regulated HLI, based on the muscle having intact, or reduced, IL-21/IL21R signaling. In comparison, 200 mRNAs...

We built a whole‐body computational model to study the role of poorly understood vascular endothelial growth factor (VEGF) 165b splice isoform in peripheral artery disease (PAD). This was and validated using published new experimental data from cells, mice, humans, explicitly accounts for known properties VEGF : lack extracellular matrix (ECM)‐binding weak phosphorylation receptor‐2 (VEGFR2) vitro . The resulting captures all information about distribution signaling human PAD, provides...

Macrophage plays a crucial role in promoting perfusion recovery and revascularization after ischemia through anti-inflammatory polarization, process essential for the treatment of peripheral arterial disease (PAD). Mitochondrial dynamics, particularly regulated by fission protein DRP1, are closely linked to macrophage metabolism inflammation. However, DRP1 reparative neovascularization remains unexplored. Here we show that expression was increased F4/80+ macrophages within ischemic muscle at...

Background: Helicobacter species are best known for their roles in the pathology of gastritis; however, several also colonize intestine, and less is about effects on development intestinal inflammation. To evaluate contributions inflammatory bowel disease, we investigated whether how pre-existing colonization would affect disease severity biomarkers inflammation experimental IBD. Materials Methods: Mice were infected with H. muridarum 2 weeks prior to induction colitis mediated by 3% dextran...

Background: Atherosclerotic occlusions in lower limbs cause ischemia that results Peripheral artery disease. Despite functional mitochondria, normal endothelial cells use Glycolysis as the primary metabolic pathway for cellular maintenance. While mitochondrial anomalies are extensively studied skeletal muscle myocytes PAD, role of mitochondria regulating ischemic (EC) function is largely unknown. Rationale: Based on a recent study showed Mitochondrial OxPhos required EC migration, we aimed...

Abstract Background: VEGF 165 a increases the expression of microRNA-17-92 cluster, promoting developmental, retinal, and tumor angiogenesis. We have previously shown that b, an alternatively spliced VEGF-A isoform, inhibits VEGFR-STAT3 pathway in ischemic endothelial cells (ECs) to decrease their angiogenic capacity. In macrophages (Møs), b VEGFR1 induce S100A8/A9 expression, which drives M1-like polarization. Our current study aims determine whether inhibition promotes perfusion recovery...

ABSTRACT In the preclinical model of peripheral arterial disease (PAD), M2-like anti-inflammatory macrophage polarization and angiogenesis are required for revascularization. The regulation cell metabolism inflammation in macrophages is tightly linked to mitochondrial dynamics. Drp1, a fission protein, has shown context-dependent phenotypes with both pro- characteristics. However, role Drp1 reparative neovascularization remains unexplored. Here we show that expression was significantly...