Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Therapeutic vascular growth in the treatment of peripheral and myocardial ischemia has not yet fulfilled its expectations in clinical trials. Randomized, double-blinded placebo-controlled trials have predominantly shown the safety and feasibility but not the clear-cut clinically relevant efficacy of angiogenic gene or recombinant growth factor therapy. It is likely that growth factor levels achieved with single injections of recombinant protein or naked plasmid DNA are too low to induce any relevant angiogenic effects. Also, the route of administration of gene transfer vectors has not been optimal in many cases leading to low gene-transfer efficacy. Animal experiments using intramuscular or intramyocardial injections of adenovirus encoding vascular endothelial growth factor (VEGF, VEGF-A), the mature form of VEGF-D, and fibroblast growth factors (FGF-1, -2, and -4) have shown high angiogenic efficacy. Adenoviral overexpression of VEGF receptor-2 ligands, VEGF-A and the mature form of VEGF-D, enlarge the preexisting capillaries in skeletal muscle and myocardium via nitric oxide(NO)-mediated mechanisms and via proliferation of both endothelial cells and pericytes, resulting in markedly increased tissue perfusion. VEGF also enhances collateral growth, which is probably secondary to increased peripheral capillary blood flow and shear stress. As a side effect of VEGF overexpression and rapid microvessel enlargement, vascular permeability increases and may result in substantial tissue edema and pericardial effusion in the heart. Because of the transient adenoviral gene expression, the majority of angiogenic effects and side effects return to baseline by 2 weeks after the gene transfer. In contrast, VEGF overexpression lasting over 4 weeks has been shown to induce the growth of a persistent vascular network in preclinical models. To improve efficacy, the choice of the vascular growth factor, gene transfer vector, and route of administration should be optimized in future clinical trials. This review is focused on these issues.
 ...
PMID:Gene transfer for therapeutic vascular growth in myocardial and peripheral ischemia. 1552 34

The discovery of the vascular endothelial growth factor (VEGF) family members VEGF, VEGF-B, placental growth factor (PlGF), VEGF-C and VEGF-D and their receptors VEGFR-1, -2 and -3 has provided tools for studying the vascular system in development as well as in diseases ranging from ischemic heart disease to cancer. VEGF has been established as the prime angiogenic molecule during development, adult physiology and pathology. PlGF may primarily mediate arteriogenesis, the formation of collateral arteries from preexisting arterioles, with potential future therapeutic use in for example occlusive atherosclerotic disease. VEGF-C and VEGF-D are primarily lymphangiogenic factors, but they can also induce angiogenesis in some conditions. While many studies have addressed the role of angiogenesis and the blood vasculature in human physiology, the lymphatic vascular system has until recently attracted very little attention. In this review, we will discuss recent advances in angiogenesis research and provide an overview of the molecular players involved in lymphangiogenesis.
 ...
PMID:The biology of vascular endothelial growth factors. 1566 81

The discovery of vascular endothelial growth factors (VEGFs) and their receptors has considerably improved the understanding of the development and function of endothelial cells. Each member of the VEGF family appears to have a specific function: VEGF-A induces angiogenesis (i.e. growth of new blood vessels from preexisting ones), placental growth factor mediates both angiogenesis and arteriogenesis (i.e. the formation of collateral arteries from preexisting arterioles), VEGF-C and VEGF-D act mainly as lymphangiogenic factors. The study of the biology of these endothelial growth factors has allowed a major progress in the comprehension of the genesis of the vascular system and its abnormalities observed in various pathologic conditions (atherosclerosis and coronary artery disease). The role of VEGF in the atherogenic process is still unclear, but actual evidence suggests both detrimental (development of a neoangiogenetic process within the atherosclerotic plaque) and beneficial (promotion of collateral vessel formation) effects. VEGF and other angiogenic growth factors (fibroblast growth factor), although initially promising in experimental studies and in initial phase I/II clinical trials in patients with ischemic heart disease or peripheral arterial occlusive disease, have subsequently failed to show significant therapeutic improvements in controlled clinical studies. Challenges still remain about the type or the combination of angiogenic factors to be administered, the form (protein vs. gene), the route, and the duration of administration.
 ...
PMID:Vascular endothelial growth factors in cardiovascular medicine. 1900 27

Twenty-six iliac artery segments were divided in two groups: atherosclerotic (A) and nonatherosclerotic (NA). Expression of LYVE-1, VEGF-C, VEGF-D, and CCR7 receptor were studied with immunohistochemistry (IHC) and Western blot (WB). IHC was performed on 26 samples of iliac arteries obtained from deceased 19 organ donors. The samples were divided into an atherosclerotic group (A) [subjects with history of cardiovascular disease (hypertension, ischemic heart disease) or/and diabetes] (n=16), and a nonatherosclerotic group (NA) [subjects without any known cardiovascular diseases or cardiovascular risk factors] (n=10). WB was performed on 19 iliac artery segments obtained from two groups, based on clinical data: an atherosclerotic group (A) [patients with atherosclerosis, who underwent surgery for lower limb ischemia] (n=10), and a nonatherosclerotic group (NA) [deceased organ donors without cardiovascular diseases/risk factors (n=9)]. Expression of LYVE-1, VEGF-C, VEGF-D, and CCR-7 was increased in atherosclerotic arteries. Positive correlations between LYVE-1 and VEGF-C expression in the intima-media complex assessed by IHC: (r=0.54; p=0.005) and WB: (r=0.47; p=0.005) were found. Positive correlations between expression of CCR-7 and other markers were observed. Lymphangiogenesis is enhanced within the atherosclerotic arterial wall. Our results confirm lymphatic system activation with increased lymphangiogenesis and lymphocyte/macrophage trafficking in atherosclerosis.
 ...
PMID:Arterial wall lymphangiogenesis is increased in the human iliac atherosclerotic arteries: involvement of CCR7 receptor. 2549 80