Differences in myocardial and peripheral VEGF and KDR levels after acute ischemia

Miraliakbari, Reza; Francalancia, Nicola A.; Lust, Robert M.; Gerardo, Jamie A; Ng, Peter; Sun, You Su; Chitwood, W. Randolph

doi:10.1016/s0003-4975(00)01375-8

Cited by 21 publications

(20 citation statements)

References 23 publications

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“…These protein levels are likely to underestimate local VEGF concentrations adjacent to transgenic keratinocytes because the whole ear, including dermis, muscle, and cartilage, was homogenized. This level of VEGF protein induction is similar to that reported from ischemic hearts or brains (Banai et al 1994;Lee et al 1999Lee et al , 2000bMiraliakbari et al 2000). As such, inadequate induction of VEGF mRNA or VEGF protein cannot explain the lack of baseline leakage mediated by HIF-1␣⌬ODD overexpression.…”

Section: Determination Of Total Vegf Mrna and Protein Expressionsupporting

confidence: 85%

“…The levels of VEGF mRNA in ear skin of K14-HIF-1␣⌬ODD transgenic mice is similar to the 13-to 25-fold elevation of VEGF expression produced by hypoxia in cultured cells (Ikeda et al 1995;Levy et al 1995Levy et al , 1996bStein et al 1998). HIF-1␣⌬ODD-mediated VEGF mRNA induction is within range, although higher, than the 2.5-to 8-fold increase in VEGF mRNA levels in hypoxic tissues (Banai et al 1994;Lee et al 1999;Miraliakbari et al 2000). These differences may be due to sensitivity of the real-time RT-PCR used here, compared with the Northern analysis used in prior work.…”

Section: Determination Of Total Vegf Mrna and Protein Expressionmentioning

confidence: 77%

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Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α

Elson¹,

Thurston²,

Huang³

et al. 2001

Genes Dev.

280

222

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Hypoxia-inducible factor-1␣ (HIF-1␣) transactivates genes required for energy metabolism and tissue perfusion and is necessary for embryonic development and tumor explant growth. HIF-1␣ is overexpressed during carcinogenesis, myocardial infarction, and wound healing; however, the biological consequences of HIF-1␣ overexpression are unknown. Here, transgenic mice expressing constitutively active HIF-1␣ in epidermis displayed a 66% increase in dermal capillaries, a 13-fold elevation of total vascular endothelial growth factor (VEGF) expression, and a six-to ninefold induction of each VEGF isoform. Despite marked induction of hypervascularity, HIF-1␣ did not induce edema, inflammation, or vascular leakage, phenotypes developing in transgenic mice overexpressing VEGF cDNA in skin. Remarkably, blood vessel leakage resistance induced by HIF-1␣ overexpression was not caused by up-regulation of angiopoietin-1 or angiopoietin-2. Hypervascularity induced by HIF-1␣ could improve therapy of tissue ischemia.

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Section: Determination Of Total Vegf Mrna and Protein Expressionsupporting

confidence: 85%

Section: Determination Of Total Vegf Mrna and Protein Expressionmentioning

confidence: 77%

Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α

Elson¹,

Thurston²,

Huang³

et al. 2001

Genes Dev.

280

222

View full text Add to dashboard Cite

show abstract

“…[94][95][96]292,[323][324][325] These protective mechanisms include the up-regulation of pro-angiogenic factors such as isoform 164 of VEGF-A that protect against capillary rarefaction, and increased expression of matrix metalloproteinases that effect repair and protect against fibrosis by degrading extracellular matrix. 326,327 In addition, short-term exposure to hypoxia leads to increased renal expression of antioxidants such as nuclear factor erythroid 2-related factor 2, hemeoxygenase 1, and metallothionein I that protect against fibrosis and inflammation induced by reactive oxygen species. 94,292,[328][329][330] However, when hypoxia is prolonged, there is an up-regulation of natural antisense HIF-1α that decreases HIF-1α expression by destabilizing its mRNA.…”

Section: The Hypoxia Death Cyclementioning

confidence: 99%

Hypoxia: The Force that Drives Chronic Kidney Disease

Colgan

Shelley

2016

Clinical Medicine & Research

125

111

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In the United States the prevalence of end-stage renal disease (ESRD) reached epidemic proportions in 2012 with over 600,000 patients being treated. The rates of ESRD among the elderly are disproportionally high. Consequently, as life expectancy increases and the baby-boom generation reaches retirement age, the already heavy burden imposed by ESRD on the US health care system is set to increase dramatically. ESRD represents the terminal stage of chronic kidney disease (CKD). A large body of evidence indicating that CKD is driven by renal tissue hypoxia has led to the development of therapeutic strategies that increase kidney oxygenation and the contention that chronic hypoxia is the final common pathway to end-stage renal failure. Numerous studies have demonstrated that one of the most potent means by which hypoxic conditions within the kidney produce CKD is by inducing a sustained inflammatory attack by infiltrating leukocytes. Indispensable to this attack is the acquisition by leukocytes of an adhesive phenotype. It was thought that this process resulted exclusively from leukocytes responding to cytokines released from ischemic renal endothelium. However, recently it has been demonstrated that leukocytes also become activated independent of the hypoxic response of endothelial cells. It was found that this endothelium-independent mechanism involves leukocytes directly sensing hypoxia and responding by transcriptional induction of the genes that encode the β2-integrin family of adhesion molecules. This induction likely maintains the long-term inflammation by which hypoxia drives the pathogenesis of CKD. Consequently, targeting these transcriptional mechanisms would appear to represent a promising new therapeutic strategy.

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“…[3][4][5] Furthermore, a differential pattern of expression has been reported for VEGF and its KDR receptors, depending on whether acute ischemia supervenes in the heart or skeletal muscle. 6 Information regarding the expression pattern of growth factors in chronic peripheral vascular disease remains elusive. Whether vascular mitogens are modulated under these conditions represents an important issue from a clinical point of view.…”

mentioning

confidence: 99%

Reversal of Angiogenic Growth Factor Upregulation by Revascularization of Lower Limb Ischemia

Porcu

Emanueli²,

Kapatsoris³

et al. 2002

Circulation

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Background — Tissue kallikrein (tK) and vascular endothelial growth factor (VEGF) are potent angiogenic agents. Upregulation of tK or VEGF was documented in animal models of acute ischemia, yet it remains unknown whether these endothelial cell mitogens are overexpressed in chronic peripheral vascular insufficiency. Methods and Results — Circulating tK and VEGF were measured in 36 patients with symptomatic peripheral vascular disease before and after surgical revascularization. In 6 patients without symptoms at rest, tK was assayed after exercise stress test. VEGF levels fell within the normal range in all patients (96±11 versus 109±13 pg/mL in healthy control subjects, P =NS) and remained unchanged after revascularization. In contrast, tK expression was upregulated in 34 of 36 patients (1107±203 versus 85±10 pg/mL in control subjects, P <0.05), with no further increase after exercise. Tissue kallikrein levels in the venous effluent of ischemic limbs were found to be positively correlated with the number of angiographically recognizable collateral vessels ( P <0.001). Follow-up studies documented reversal of tK upregulation after revascularization ( P <0.01), whereas no change was observed in venous samples from untouched legs. Conclusions — Induction of tK could represent a compensatory response to chronic arterial insufficiency, attempting to maintain an adequate tissue perfusion. Heterogeneous statement of growth factors may have important implications in reparative and therapeutic angiogenesis.

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Differences in myocardial and peripheral VEGF and KDR levels after acute ischemia

Cited by 21 publications

References 23 publications

Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α

Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1α

Hypoxia: The Force that Drives Chronic Kidney Disease

Reversal of Angiogenic Growth Factor Upregulation by Revascularization of Lower Limb Ischemia

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