Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with acromegaly have significant morbidity and mortality, associated with cardiovascular disease. Acromegaly is often complicated by other diseases such as diabetes mellitus, hypertension, and coronary artery disease, so the existence of acromegalic cardiomyopathy remains uncertain. Cardiac performance was investigated in patients with uncomplicated acromegaly. A subgroup of hypertensive acromegalics was also studied. In addition, the effects of chronic octreotide therapy or surgery on cardiac structure and function in acromegaly were studied. Twenty-six patients and 15 healthy controls underwent gated blood-pool cardiac scintigraphy and echocardiography at rest and during exercise. Echocardiography was repeated after 6 months of octreotide therapy (n = 11). Cardiac scintigraphy was repeated after 12 and 24 months of octreotide therapy (n = 10) or 12 to 24 months after surgery (n = 8). ECG, blood pressure, and heart rate were monitored during cardiac scintigraphy. Left ventricular mass (LVM) was calculated from the findings of the echocardiography. Serum growth hormone (GH) levels and plasma insulin-like growth factor-1 (IGF-1) levels were monitored. LVM index was significantly higher (P < .003) in acromegalics than controls and in hypertensive acromegalics than normotensives, but all other indices of cardiac function were similar. Chronic octreotide decreased GH and IGF-1 levels and improved the structural abnormalities as measured by echocardiography. Chronic octreotide or surgery did not alter cardiac function parameters. Thus, important changes in cardiac structure and function occur in uncomplicated acromegaly, and improvements can be demonstrated after chronic octreotide therapy. Heart disease in acromegaly appears to be secondary to high circulating GH levels.
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PMID:Cardiovascular aspects in acromegaly: effects of treatment. 876 83

Serum insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and a range of growth and nutritional variables were investigated in 62 infants with congenital heart disease and healthy controls. Infants with congenital heart disease were small, underweight, and had a reduced energy intake. Serum IGF-1 and IGFBP-3 concentrations were significantly reduced. Decreased IGF-1 and IGFBP-3 levels are observed in nutritional deficiency; similar findings in congenital heart disease suggest that undernutrition contributes to the poor growth of these infants. Serial measurements of serum IGF-1 and IGFBP-3 may be helpful in monitoring the effect of nutritional treatment in congenital heart disease.
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PMID:Serum insulin-like growth factor 1 in congenital heart disease. 886 2

We employed cDNA microarrays representing 4000 distinct sequences to profile changes in gene expression in a rodent model of heart disease, namely, progression to heart failure after myocardial infarction. Differential gene expression in the left ventricle was examined at 4-week intervals over a 12-week period after coronary artery ligation in rats. Over this time course, insulin-like growth factor-binding protein-3 (IGFBP-3) was found to have a greater expression than in nondiseased tissues. We then employed quantitative real-time PCR to analyze gene expression in neonatal rat cardiac myocytes that had been treated with recombinantly expressed IGFBP-3 to examine a number of transcriptional responses designed to reflect the heart failure phenotype. The IGFBP-3 protein was shown to induce transcription of atrial natriuretic factor (ANF) and beta-myosin heavy chain (B-MHC). Analysis of conditioned media taken from IGFBP-3-treated cardiac myocyte cultures demonstrated an increase in ANF protein as well as in protein synthesis, as determined by metabolic incorporation of a radiolabeled amino acid. However, transcriptional changes of troponin-1, endothelin-1, or angiotensin-II by IGFBP-3 were not observed.
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PMID:Insulin-like growth factor-binding protein-3 induces fetalization in neonatal rat cardiomyocytes. 1117 73

Variation in the circulating concentrations of the insulin-like growth factor (IGF) system has been implicated in the etiology of chronic diseases including cancer (prostate, breast, colon, and lung), heart disease, type 2 diabetes, and osteoporosis. We searched for sociodemographic, anthropometric, reproductive, lifestyle, and dietary determinants of IGF-I and insulin-like growth factor binding protein (IGFBP) -3 serum concentrations. Serum samples were collected in a Singapore Chinese cohort with a mean age of 61 years. Subject information was assessed during an in-person interview. Radioimmunometrically measured IGF-I and IGFBP-3 concentrations were available for 312 men and 326 postmenopausal women ages 50 years or older. Mean IGF-I concentrations were 144 ng/ml and 121 ng/ml for men and women, respectively (gender difference, P < 0.0001), and mean IGFBP-3 concentrations were 3710 ng/ml and 4147 ng/ml for men and women, respectively (gender difference, P < 0.0001). IGF-I and IGFBP-3 decreased with age (P for trend <0.0001); the age-related decrease in the IGF-I:IGFBP-3 molar ratio was stronger in women than men. IGF-I concentrations were higher among physically inactive subjects and among women with an early age at menarche. Consumption of saturated fat was found to decrease, and intake of omega-3 polyunsaturated fatty acids and of dietary fiber was found to increase circulating IGFBP-3 concentrations. Intake of calcium from food and supplement was associated positively with circulating IGF-I, IGFBP-3, and molar ratio. Intake of soy was associated positively with IGF-I and molar ratio concentrations, but only in men. The results of this study lend additional support to the hypothesis that circulating IGF-I concentrations increase the risk of prostate, bladder, colorectal, and breast cancer.
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PMID:Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women. 1291 5

Secretory clusterin protein (sCLU) is a general genotoxic stress-induced, pro-survival gene product implicated in aging, obesity, heart disease, and cancer. However, the regulatory signal transduction processes that control sCLU expression remain undefined. Here, we report that induction of sCLU is delayed, peaking 72 h after low doses of ionizing radiation, and is dependent on the up-regulation of insulin-like growth factor-1 as well as phosphorylation-dependent activation of its receptor (IGF-1 and IGF-1R, respectively). Activated IGF-1R then stimulates the downstream Src-Mek-Erk signal transduction cascade to ultimately transactivate the early growth response-1 (Egr-1) transcription factor, required for sCLU expression. Thus, ionizing radiation exposure causes stress-induced activation of IGF-1R-Src-Mek-Erk-Egr-1 signaling that regulates the sCLU pro-survival cascade pathway, important for radiation resistance in cancer therapy.
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PMID:Delayed activation of insulin-like growth factor-1 receptor/Src/MAPK/Egr-1 signaling regulates clusterin expression, a pro-survival factor. 1568 20

Exposure to environmental tobacco smoke has been epidemiologically linked to heart disease among nonsmokers. However, the molecular mechanism behind the pathogenesis of cardiac disease is unknown. In this study, we found that Wistar rats, exposed to tobacco cigarette smoke at doses of 5, 10, or 15 cigarettes for 30 min twice a day for 1 month, had a dose-dependently reduced heart weight to body weight ratio and enhanced interstitial fibrosis as identified by histopathologic analysis. The mRNA and activity of matrix metalloprotease-2 (MMP-2), representing the progress of cardiac remodeling, were also elevated in the heart. In addition, we used reverse-transcriptase polymerase chain reaction and Western blotting to demonstrate significantly increased levels of the apoptotic effecter caspase-3 in treated animal hearts. Dose-dependently elevated mRNA and protein levels of Fas, and promoted apoptotic initiator caspase-8 (active form), a molecule of a death-receptor-dependent pathway, coupled with unaltered or decreased levels of cytosolic cytochrome c and the apoptotic initiator caspase-9 (active form), molecules of mitochondria-dependent pathways, may be indicative of cardiac apoptosis, which is Fas death-receptor apoptotic-signaling dependent, but not mitochondria pathway dependent in rats exposed to second-hand smoke (SHS). With regard to the regulation of survival pathway, using dot blotting, we found cardiac insulin-like growth factor-1 (IGF-1) and IGF-1 receptor mRNA levels to be significantly increased, indicating that compensative effects of IGF-1 survival signaling could occur. In conclusion, we found that the effects of SHS on cardiomyocyte are mediated by the Fas death-receptor-dependent apoptotic pathway and might be related to the epidemiologic incidence of cardiac disease of SHS-exposed nonsmokers.
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PMID:Second-hand smoke-induced cardiac fibrosis is related to the Fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats. 1620 45

Coronary heart disease (CHD) is a preventable disease with high morbidity and mortality. Largely omitted from the efforts at detection and treatment are the contributions of the lungs, the skeletal muscles and the arteries to heart disease pathology. Also omitted are the effects of the age-related decline in insulin-like growth factor-1 (IGF-1) and the age-related increase in cell membrane pathology. The hypothesis on which this model is based postulates that growing older, over time, necessarily results in pathological changes in the heart, the lungs, the skeletal muscles and the arteries. Additionally, the age-related decline in (IGF-1) that occurs in the otherwise healthy aged population also causes similar pathological changes. The drug portion of the proposed treatment includes the use of the drug acetyl-l-carnitine (ALC) to increase the age-related decreased IGF-1 levels. The drug centrophenoxine (CPH) is used to reverse the age-related pathological changes that inevitably occur in the heart, the lungs, the skeletal muscles and the arteries. A testing procedure is included to improve the detection of heart disease and to monitor the results. It consists of five tests: the monitoring of plasma IGF-1 levels; the monitoring of blood pressure, and in particular elevated systolic blood pressure; the monitoring of blood pressure variability over time; a heart rate recovery time test and a heart rate reserve test. Heart rate reserve is defined as the difference between maximal heart rate and resting heart rate, after treadmill exercise. The changes in test results noted during treatment are an indicator of progress or deterioration in the prevention of heart disease, whatever the case may be.
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PMID:An adjunctive preventive treatment for heart disease and a set of diagnostic tests to detect it: insulin-like growth factor-1 deficiency and cell membrane pathology are an inevitable cause of heart disease. 1641 84

The injured mammalian heart is particularly susceptible to tissue deterioration, scarring, and loss of contractile function in response to trauma or sustained disease. We tested the ability of a locally acting insulin-like growth factor-1 isoform (mIGF-1) to recover heart functionality, expressing the transgene in the mouse myocardium to exclude endocrine effects on other tissues. supplemental mIGF-1 expression did not perturb normal cardiac growth and physiology. Restoration of cardiac function in post-infarct mIGF-1 transgenic mice was facilitated by modulation of the inflammatory response and increased antiapoptotic signaling. mIGF-1 ventricular tissue exhibited increased proliferative activity several weeks after injury. The canonical signaling pathway involving Akt, mTOR, and p70S6 kinase was not induced in mIGF-1 hearts, which instead activated alternate PDK1 and SGK1 signaling intermediates. The robust response achieved with the mIGF-1 isoform provides a mechanistic basis for clinically feasible therapeutic strategies for improving the outcome of heart disease.
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PMID:Enhancing repair of the mammalian heart. 1752 68

Although numerous studies have explored the relation of insulin-like growth factor (IGF)-I and IGF-binding protein (BP) 3 with cancer and cardiovascular disease, only two previous studies are known to have looked at the association of IGF-I and IGF-BP3 with risk of mortality. The objective of this US study was to examine the risk of all-cause, heart disease, and cancer mortality associated with IGF-I and IGF-BP3 levels using data from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES III Mortality Study (n = 6,061) (1988-2000). The authors constructed proportional hazards models with age as the time scale to determine the association of baseline IGF-I and IGF-BP3 levels with subsequent mortality. After adjustment for baseline measures, there was no increased risk of all-cause, heart disease, or cancer mortality for the lower quartiles of IGF-I compared with the highest quartile. The adjusted relative hazard of all-cause mortality for the lowest quartile of IGF-BP3 compared with the highest quartile was 1.57 (95% confidence interval: 0.98, 2.52), and the trend for risk was significant (p = 0.0364), but there was no increased risk of heart disease or cancer mortality. Results suggest that the association of IGF-I and IGF-BP3 with mortality may differ from associations with incidence of disease.
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PMID:Insulin-like growth factors and subsequent risk of mortality in the United States. 1760 36

In this study we aimed to evaluate serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) levels in children with congenital heart disease (CHD) and to determine if these parameters have any relationship to the cyanosis, nutritional status and the left ventricular systolic function. This study is prospective-randomized study which conducted in 94 CHD patients (36 girls and 58 boys, aged between one 1-192 months, 19 cyanotic CHD and 75 acyanotic CHD) and age-sex matched 54 children (26 girls and 28 boys) with no CHD. In the study group, 37 out of the 94 CHD patients (39.4%) and 16 out of the 54 controls (29.6%) had malnutrition. The difference between the cyanotic and acyanotic patients in respect to malnutrition was significant (57.9% and 34.6%, p<0.05). Serum IGF-1 levels were lower (41.8+/-3.9 microg/L, 106.9+/-17.9 microg/L respectively, p<0.001) and GH levels were higher (6.43+/-0.9 ng/ml, 3.87+/-0.5 respectively, p<0.05) in CHD patient group than the controls. Serum IGF-1 levels were significantly lower in cyanotic CHD patients than the acyanotic patients (17.2+/-3.2 microg/L, 48.7.0+/-4.6 microg/L respectively, p<0.001) and serum IGF-1 levels were both lower in acyanotic and cyanotic CHD patients than the controls (p<0.001 for both). Serum IGF-1 and GH levels were similar between the well-nourished CHD patients and CHD patients with malnutrition (p>0.05). In total study group, the most effective factors on serum IGF-1 levels was presence of CHD (p<0.001), in CHD patients, the presence of cyanosis is the most effective factor on serum IGF-1 level, the presence of malnutrition is the most effective factor on serum IGFBP-3 levels (p<0.01). In the acyanotic, cyanotic, and the entire CHD patient groups, we find no correlations between the serum IGF-1, IGFBP-3 levels and left ventricular systolic function measurements. But serum GH levels were negatively correlated with diastolic left ventricular interseptum diameter, diastolic left ventricular mass and left ventricular end-diastolic volume measurements in CHD patients. In conclusion, we determined that the most important factor on serum IGF-1 levels is cyanosis. Reduced IGF1 levels and decreased left ventricular mass with an elevated GH levels in CHD patients and these findings are prominent in the cases with cyanosis and malnutrition. For this reason we believe that chronic hypoxia plays a significant role in the pathogenesis of malnutrition and also we believe that IGF-1 deficiency seen in CHD patients may be responsible in the etiology of the decrease in left ventricular mass independently from GH.
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PMID:Serum IGF-1, IGFBP-3 and growth hormone levels in children with congenital heart disease: relationship with nutritional status, cyanosis and left ventricular functions. 1762 62


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