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)

In the human fetus IGFBP-3 mRNA expression is most abundant in the skin, muscle and heart but circulating IGFBP-3 levels show age-related variations. In human heart tissues from controls and patients with either ischemic, dilated or hypertrophic cardiomyopathy (no.: 20, age-range from fetuses to elderly subjects) we determined the expression of cardiac IGFBP-3 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and the protein by Western blotting. The same parameters were also determined in human livers. We detected IGFBP-3 mRNA in neonatal and adult as well as in fetal human heart tissues in both ventricles. Western blotting revealed the presence of IGFBP-3 in all the examined cardiac tissues. IGFBP-3 appeared to be more abundant in the heart than in the liver and in the failing hearts from patients with ischemic heart disease than in those with hypertrophic cardiomyopathy. Thus both normal and pathological human heart tissues express IGFBP-3 across lifespan and IGFBP-3 could play IGF-dependent and/or -independent actions at the myocardial level.
 ...
PMID:Neonatal and adult human heart tissues from normal subjects and patients with ischemic, dilated or hypertrophic cardiomyopathy express insulin-like growth factor binding protein-3 (IGFBP-3). 1119 4

Current guidelines for the diagnosis of adult growth hormone deficiency (GHD) state that the diagnosis must be proven biochemically by provocative testing that is done within the appropriate clinical context. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 h and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. The insulin tolerance test (ITT) is the test of choice, with severe GHD being defined by a GH peak less than 3 microg/l, the cut-off that distinguishes normal from GHD adults. The ITT is contraindicated in the presence of ischemic heart disease, seizure disorders, and in the elderly. Other tests are as reliable as the ITT, provided they are used with appropriate cut-off limits. Glucagon stimulation, a classical test, and especially new maximal tests such as GHRH in combination with arginine or GHS (i.e., GHRP-6) have well-defined cut-off limits, are reproducible, are independent of age and gender, and are able to distinguish between normal and GHD subjects. The confounding effect of overweight or obesity on the interpretation of the GH response to provocative tests needs to be considered as the somatotropic response to all stimuli is negatively correlated with body mass index. Appropriate cut-offs for lean, overweight, and obese subjects must be used in order to avoid false-positive diagnoses of severe GHD in obese adults.
 ...
PMID:Growth hormone levels in the diagnosis of growth hormone deficiency in adulthood. 1742 91

Insulin-like growth factors (IGF-I and II) are important endocrine, paracrine and autocrine mediators of physiological growth. They promote cellular proliferation, survival and differentiation. Their effects are mediated mainly through the IGF-I receptor, but IGFs also bind to the IGF-II/mannose 6-phosphate and insulin receptors. IGF activity is modulated by a family of six high-affinity IGF binding proteins (IGFBPs); in most situations, IGFBPs inhibit IGF actions but they may also enhance them. Assays are now available for IGF-I, IGF-II and individual IGFBPs. IGF-I and IGFBP-3 assays have some utility in the diagnosis and management of acromegaly and growth hormone deficiency. There is a large body of in vitro and in vivo evidence supporting a pathogenic role for alterations in the IGF system in many diseases, including diabetes, cancer, cardiovascular disease and neuromuscular disease. More recently, epidemiological studies have linked high IGF-I levels with some cancers and low IGF-I levels with ischaemic heart disease. Preliminary studies of recombinant IGF-I as a treatment for diabetes, osteoporosis and neuromuscular disease have been performed in humans. In contrast, there is considerable interest in developing IGF inhibitors for the treatment of cancer. This apparent paradox highlights the need to develop therapeutics beyond the natural ligands and inhibitors, with characteristics such as ligand and tissue specificity. This will only become possible as we increase our understanding of this complex system. Additionally, as IGF and IGFBP assays are becoming more readily available, their role in the diagnosis and monitoring of diseases should be more clearly defined in the near future.
 ...
PMID:The insulin-like growth factor system: towards clinical applications. 1845 8

Cardiac atrial appendage stem cells (CASCs) show extraordinary myocardial differentiation properties, making them ideal candidates for myocardial regeneration. However, since the myocardium is a highly vascularized tissue, revascularization of the ischemic infarct area is essential for functional repair. Therefore, this study assessed if CASCs contribute to cardiac angiogenesis via paracrine mechanisms. First, it was demonstrated that CASCs produce and secrete high levels of numerous angiogenic growth factors, including vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and insulin-like growth factor binding protein 3 (IGFBP-3). Functional in vitro assays with a human microvascular endothelial cell line (HMEC-1) and CASC CM showed that CASCs promote endothelial cell proliferation, migration and tube formation, the most important steps of the angiogenesis process. Addition of inhibitory antibodies against identified growth factors could significantly reduce these effects, indicating their importance in CASC-induced neovascularization. The angiogenic potential of CASCs and CASC CM was also confirmed in a chorioallantoic membrane assay, demonstrating that CASCs promote blood vessel formation in vivo. In conclusion, this study shows that CASCs not only induce myocardial repair by cardiomyogenic differentiation, but also stimulate blood vessel formation by paracrine mechanisms. The angiogenic properties of CASCs further strengthen their therapeutic potential and make them an optimal stem cell source for the treatment of ischemic heart disease.
 ...
PMID:Cardiac atrial appendage stem cells promote angiogenesis in vitro and in vivo. 2729 Oct 64