A5032735264- Adipose Tissue and Metabolism
- Angiogenesis and VEGF in Cancer
- FOXO transcription factor regulation
- Adipokines, Inflammation, and Metabolic Diseases
- Barrier Structure and Function Studies
- Single-cell and spatial transcriptomics
- Lymphatic System and Diseases
- Peripheral Artery Disease Management
- Cardiovascular Disease and Adiposity
- Sex and Gender in Healthcare
- Cancer Cells and Metastasis
- Cancer-related molecular mechanisms research
- Hippo pathway signaling and YAP/TAZ
- Muscle Physiology and Disorders
- Dietary Effects on Health
- High Altitude and Hypoxia
- Aortic Disease and Treatment Approaches
- Sunflower and Safflower Cultivation
- Caveolin-1 and cellular processes
- Ferroptosis and cancer prognosis
- Atherosclerosis and Cardiovascular Diseases
- Muscle and Compartmental Disorders
- Transplantation: Methods and Outcomes
- Cell Adhesion Molecules Research
- Apelin-related biomedical research
Uppsala University
2022-2025
Science for Life Laboratory
2022-2025
York University
2013-2022
Dysfunctional and leaky blood vessels resulting from disruption of the endothelial cell (EC) barrier accompanies numerous diseases. The EC is established through tight adherens junctions. However, expression pattern precise contribution different junctional proteins to poorly understood. Here, we focus on organs with continuous endothelium identify structural functional in vivo characteristics barrier. Assembly multiple single-cell RNAseq datasets into a single integrated database revealed...
Vascular endothelial (VE)-cadherin in adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated diseases such as cancer retinopathies. Inhibitors Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin phosphorylation prevent excessive leakage, edema high interstitial pressure. Here we show that Src-related Yes kinase, rather than Src, localized at cell (EC) where it becomes activated a flow-dependent manner....
Endothelial phospholipase Cγ (PLCγ) is essential for vascular development; however, its role in healthy, mature, or pathological vessels unexplored. Here, we show that PLCγ was prominently expressed of several human cancer forms, notably renal cell carcinoma (RCC). High expression clear RCC correlated with angiogenic activity and poor prognosis, while low immune activation. induced downstream endothelial growth factor receptor 2 (VEGFR2) phosphosite Y1173 (pY1173). Heterozygous...
Impaired angiogenesis is a hallmark of metabolically dysfunctional adipose tissue in obesity. However, the underlying mechanisms restricting within this context remain ill-defined. Here, we demonstrate that induced endothelial-specific depletion transcription factor Forkhead Box O1 (FoxO1) male mice led to increased vascular density tissue. Upon high-fat diet feeding, endothelial cell FoxO1-deficient exhibited even greater remodeling visceral depot, which was paralleled with healthier...
Background: Impaired capillary growth (angiogenesis) in skeletal muscle and adipose tissue contributes to the development of metabolic disorders obese males. This association remains unexplored females, despite mounting evidence that endothelial cells have sex-specific transcriptional profiles. Therefore, herein we assessed whether males females show distinct angiogenic capacities response diet-induced obesity. Methods: Age-matched male female mice were fed normal chow or high-fat obesogenic...
Key points The growth of new capillaries, angiogenesis, within skeletal muscle occurs only after weeks repeated aerobic exercise. Paradoxically, large increases in pro‐angiogenic factors such as vascular endothelial factor occur with a single exercise bout. mechanisms underlying the substantial lag angiogenic response remain to be elucidated. We detected concomitant angiostatic Forkhead Box ‘O’ transcription FoxO1 and FoxO3a matrix protein thrombospondin‐1 following bout exercise, but these...
The source of vascular endothelial growth factor-A (VEGF-A) may influence function. Exercise-induced has been attributed to elevated metabolic demand and increased blood flow, involving the production VEGF-A by skeletal muscle cells respectively. We hypothesized that muscle-derived is not required for adaptations flow in muscle, as this remodelling stimulus originates within capillary.Myocyte-specific (mVEGF(-/-) ) deleted mice were treated 7-21 days with vasodilator prazosin produce a...
Skeletal muscle microvascular dysfunction contributes to disease severity in type 2 diabetes. Recent studies indicate a role for Forkhead box O (FoxO) transcription factors modulating endothelial cell phenotype. We hypothesized that high-fat (HF) diet generates dysfunctional vascular niche through an increased expression of FoxO. FoxO1 protein (+130%) the skeletal capillaries from HF compared normal chow-fed mice. was significantly elevated cultured cells exposed saturated fatty acid...
Female mice display greater adipose angiogenesis and maintain healthier tissue than do males upon high-fat diet feeding. Through transcriptome analysis of endothelial cells (EC) from the white male female high-fat-fed for 7 weeks, we found that EC exhibited pronouncedly sex-distinct transcriptomes. Genes upregulated in were associated with proliferation, oxidative phosphorylation, chromatin remodeling contrasting dominant enrichment genes related to inflammation a senescence-associated...
Remodeling of the skeletal muscle microvasculature involves coordinated actions matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitor (TIMPs). We hypothesized that loss TIMP1 would enhance both ischemia flow-induced vascular remodeling by increasing MMP activity. deficient (Timp1-/- ) wild-type (WT) C57BL/6 mice underwent unilateral femoral artery (FA) ligation or were treated with prazosin, an alpha-1 adrenergic receptor antagonist, in order to investigate...
Critical limb ischaemia (CLI) is characterized by inadequate angiogenesis, arteriolar remodelling and chronic myopathy, which are most severe in type 2 diabetic patients. Hypertriglyceridaemia, commonly observed these patients, compromises macrovascular function. However, the effects of high-fat diet-induced increases circulating lipids on microvascular not established. Here, we investigated if diet would mimic detrimental effect diabetes post-ischaemia vascular muscle regeneration, using a...
Abstract Neuropilin-1 (NRP1) regulates endothelial cell (EC) biology through modulation of vascular growth factor receptor 2 (VEGFR2) signalling by presenting VEGFA to VEGFR2. How NRP1 impacts VEGFA-mediated hyperpermeability has however remained unresolved, described as exerting either a positive or passive function. Using EC-specific Nrp1 knock-out mice, we discover that EC-expressed exerts an organotypic role. In the ear skin, VEGFA/VEGFR2-mediated leakage was increased following loss EC...
Diabetes promotes an angiostatic phenotype in the microvascular endothelium of skeletal muscle and skin. Angiogenesis-related microRNAs (angiomiRs) regulate angiogenesis through translational repression pro- anti-angiogenic genes. The maturation micro-RNA (miRs), including angiomiRs, requires action DROSHA DICER proteins. While hyperglycemia modifies expression it is unknown whether high glucose conditions alter process angiomiRs dermal endothelial cells (MECs). Compared to 5 mM glucose,...
Idiopathic systemic capillary leak syndrome (ISCLS) is a rare, recurrent condition with dramatically increased blood vessel permeability and, therefore, induction of edema, which may lead to organ damage and death. In this issue the JCI, Ablooglu et al. showed that ISCLS vessels were hypersensitive agents known increase vascular permeability, using human biopsies, cell culture, mouse models. Several endothelium-specific proteins regulate endothelial junctions dysregulated thereby compromised...
Obesity is associated with skeletal muscle capillary rarefaction, which affects function and whole body metabolism. Endothelial forkhead box O (FoxO) transcription factors restrain angiogenesis in response to chronic endurance exercise during ischemic recovery. We hypothesized that FoxO proteins contribute obesity‐related rarefaction. Three PolyI:C injections were administered induce an endothelial directed FoxO1/3a/4deletion Mx1‐Cre + ;FoxO1/3a/4 L/L mice (FoxO Δ ) but not control ‐...
Skeletal muscle capillaries are critical determinants of nutrient delivery and utilization capillary network density is thought to correlate with insulin sensitivity. Conflicting data exist regarding the consequence obesity‐associated metabolic disturbances on skeletal capillarization, positive, negative no effect having been reported. The purpose this investigation assess influence obesity induced by high fat feeding or leptin receptor mutation, angiogenic profile within microenvironment,...
Paracrine‐derived vascular endothelial growth factor (VEGF) is established as an indispensable contributor to the angiogenic cascade. Autocrine VEGF, in contrast, solely attributed cell survival signaling, and its potential regulation of other functions has not been studied. We hypothesized that deletion VEGF would disrupt migration shear stress adaptation. Endothelial cells were isolated from transgenic mice having exon 3 flanked by loxP sites (VEGF L/L ). Cells transduced with adeno‐Cre...
Neovascularization in peripheral artery disease (PAD) is impaired despite upregulation of factors that promote blood vessel growth which suggest a concomitant increase anti‐angiogenic repressors. We previously showed depletion FoxO proteins (FoxO1/3a/4) induced angiogenesis and enhanced flow recovery mouse model PAD. The purpose this study to independently assess the roles endothelial FoxO1 synergistic actions 1 & 3a Mice with tamoxifen‐inducible specific deletions (PDGFBCreER T2 +;FoxO1...
Background and hypothesis Impaired vascular growth remodeling is implicated in the disruption of adipose tissue structure function obesity, leading to systemic metabolism dysfunction. As Forkhead Box O1 (FoxO1) transcription factor regulates endothelial cell homeostasis restrains angiogenesis, we investigated role FoxO1 development obesity using endothelium FoxO1‐deficient mice. Experimental design To generate cell‐specific deficient mice (FoxO1 iEC‐D ), conditional L/L floxed were bred with...