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)

GH exerts direct effects on myocardial growth and function. Evidence from laboratory models shows that GH (or IGF-I) induces mRNA expression for specific contractile proteins and myocyte hypertrophy. Furthermore, GH increases the force of contraction and determines myosin phenoconversion toward the low ATPase activity V3 isoform. These data provide plausible explanations for the cardiac abnormalities observed in clinical settings of excessive or defective GH production. In acromegaly, the functional consequences of GH excess initially prevail (hyperkinetic syndrome), followed by alterations of cardiac function when myocardial hypertrophy develops. This involves both ventricles and is purposeless because it occurs without increased wall stress. Hypertrophy also entails proliferation of the myocardial fibrous tissue that leads to interstitial remodeling. The functional consequence is an impaired ventricular relaxation that causes a diastolic dysfunction, followed by impairment of systolic function. In untreated disease, cardiac performance slowly but inexorably deteriorates and heart failure eventually develops. Several lines of evidence support the specificity of heart disease in acromegaly. Particularly demonstrative are the recent studies in which GH production was suppressed by octreotide, with a consequent significant regression of hypertrophy and improvement of cardiac dysfunction. It is not yet established whether full recovery of normal cardiac morphology and function is possible after correction of GH excess. The point is not a minor one since the possibility to revert, albeit partially, myocardial fibrosis is of great relevance to the control of cardiac hypertrophy in general. GHD leads to a reduced mass of both ventricles and to impaired cardiac performance with low heart rate (hypokinetic syndrome). These alterations are particularly evident during physical exercise and might provide an important contribution to the reduced exercise capacity of GHD patients, in addition to the reduced muscle mass and strength. The data also support a role of GH in the maintenance of a normal cardiac structure and performance. The hypokinetic syndrome is well documented in young patients in whom GHD began very early in their childhood. In contrast, the data in adult-onset GHD are less consistent. This suggests that the consequences of GHD are more relevant if the disorder starts during early heart development. As observed with other abnormalities associated with GHD, cardiac dysfunction is also susceptible to marked improvement by hrGH. This observation lends further support to the proposal to treat these patients with replacement therapy.
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PMID:Growth hormone and the heart. 784 68

Cardiovascular problems have long been recognized as responsible for an increased morbidity and mortality in patients with acromegaly. The aim of the present study was to evaluate echocardiographically the prevalence of cardiomyopathy in a cohort of acromegalic patients and to analyze the results in relation to demographic, clinical and hormonal data. This study, a retrospective controlled clinical trial, was performed in 25 acromegalic patients, 12 men and 13 women aged 26-66 years (mean: 52.6). Fifteen patients had an active disease, 10 were cured by previous pituitary surgery. The same echocardiographic parameters were analyzed in 50 healthy subjects aged 30-70 years (mean: 51.4). Serum GH was determined on at least 4 samples drawn over 24 hours and plasma IGF-I on a single point. Standardized parameters of diastolic and systolic function were evaluated by real-time Doppler echocardiography. Twelve patients with active acromegaly underwent also 48-hour ECG registering. Left ventricular (LV) hypertrophy was found in 14/25 patients (56%). No difference was found between patients with active disease (53%) and patients with cured acromegaly (60%). LV mass index was significantly increased in acromegalics in comparison with healthy subjects (137 +/- 43 g/m2 vs 96 +/- 16 g/m2, p < 0.01) and also the indices of LV diastolic function were significantly impaired. Asymmetric septal hypertrophy was found only in one patient. Hypertension was detected in 9/25 patients (36%) without difference between patients with active or cured disease (40% vs 30%, NS). No significant correlation was found between hormonal or clinical data and echocardiographic findings. During Holter monitoring, heart rate of acromegalics was not significantly different from that of controls (78 +/- 12 bpm vs 72 +/- 10 bpm, NS) and only isolated supraventricular or ventricular premature complexes (Lown class 1) were detected. In conclusion, this study provides evidence of subclinical LV dysfunction in acromegaly in the absence of other known causes of heart disease and no significant difference in echocardiographic pattern was apparent between active or cured acromegalics.
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PMID:Doppler echocardiographic patterns in patients with acromegaly. 865 20

Cyanotic congenital heart disease in children commonly causes more pronounced growth retardation in comparison with acyanotic congenital heart disease. Chronic hypoxemia has been suggested as the cause of poor growth in these patients, but the relationship between serum IGF-I levels and chronic hypoxemia is unclear. Serum IGF-I concentrations, oxygen saturation and nutritional status were evaluated in 29 patients with cyanotic congenital heart disease, and serum IGF-I levels were compared with a group of 20 well-nourished, age-matched control children to assess the relationship between IGF-I levels and chronic hypoxemia. The nutritional status of each patient was determined by using anthropometric parameters and calorie and protein intake ratios. The patients were divided into malnourished and well-nourished groups (21 and 8 patients, respectively) according to their nutritional status. Serum IGF-I concentrations were measured in the two patient groups and the controls. The malnourished group had the lowest IGF-I levels (48.14 +/- 21.8 ng/ml, p<0.05). However, the well-nourished group's IGF-I levels were significantly lower than the control subjects' despite improved nutritional status (85.5 +/- 30.2 and 107 +/- 19.7 ng/ml, respectively, p<0.05). In addition, we found a positive correlation between serum IGF-I levels and oxygen saturation of the patients (r=0.402, p<0.05). These findings indicate that chronic hypoxemia has a direct or indirect effect to reduce serum IGF-I concentrations and this may be a cause of the increased growth failure in patients with cyanotic congenital heart disease.
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PMID:Chronic hypoxemia leads to reduced serum IGF-I levels in cyanotic congenital heart disease. 1077 98

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

Cardiac fibrosis is a key component of heart disease and involves the proliferation and differentiation of matrix-producing fibroblasts. The effects of an antifibrotic peptide hormone, relaxin, in inhibiting this process were investigated. We used rat atrial and ventricular fibroblasts, which respond to profibrotic stimuli and express the relaxin receptor (LGR7), in addition to two in vivo models of cardiac fibrosis. Cardiac fibroblasts, when plated at low density or stimulated with TGF-beta or angiotensin II (Ang II), accelerated fibroblast differentiation into myofibroblasts, as demonstrated by significantly increased alpha-smooth muscle actin expression, collagen synthesis, and collagen deposition (by up to 95% with TGF-beta and 40% with Ang II; all P < 0.05). Fibroblast proliferation was significantly increased by 10(-8) m and 10(-7) m Ang II (63-75%; P < 0.01) or 0.1-1 microg/ml IGF-I (27-40%; P < 0.05). Relaxin alone had no marked effect on these parameters, but it significantly inhibited Ang II- and IGF-I-mediated fibroblast proliferation (by 15-50%) and Ang II- and TGF-beta-mediated fibroblast differentiation, as detected by decreased expression of alpha-smooth muscle actin (by 65-88%) and collagen (by 60-80%). Relaxin also increased matrix metalloproteinase-2 expression in the presence of TGF-beta (P < 0.01) and Ang II (P < 0.05). Furthermore, relaxin decreased collagen overexpression when administered to two models of established fibrotic cardiomyopathy, one due to relaxin deficiency (by 40%; P < 0.05) and the other to cardiac-restricted overexpression of beta2-adrenergic receptors (by 58%; P < 0.01). These coherent findings indicate that relaxin regulates fibroblast proliferation, differentiation, and collagen deposition and may have therapeutic potential in diseased states characterized by cardiac fibrosis.
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PMID:Relaxin modulates cardiac fibroblast proliferation, differentiation, and collagen production and reverses cardiac fibrosis in vivo. 1515 73

The presence of a diabetic cardiomyopathy, independent of hypertension and coronary artery disease, is still controversial. This systematic review seeks to evaluate the evidence for the existence of this condition, to clarify the possible mechanisms responsible, and to consider possible therapeutic implications. The existence of a diabetic cardiomyopathy is supported by epidemiological findings showing the association of diabetes with heart failure; clinical studies confirming the association of diabetes with left ventricular dysfunction independent of hypertension, coronary artery disease, and other heart disease; and experimental evidence of myocardial structural and functional changes. The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, changes in calcium homeostasis), myocardial fibrosis (association with increases in angiotensin II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity). This review presents evidence that diabetes is associated with a cardiomyopathy, independent of comorbid conditions, and that metabolic disturbances, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance may all contribute to the development of diabetic heart disease.
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PMID:Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. 1529 81

Can mouse genetics teach us enough about the biology of aging to guide the search for anti-aging medicines that can delay late-life illness? Recent progress gives reason for optimism, with new data showing that changes in single genes can extend average and maximal life span by 40%. Mice with these genetic variants remain healthy, active, and cognitively intact at average ages that correspond to 110-120 years of human life span. Multiple lines of evidence now point to a hormone, IGF-I, as a key influence on life span, with low IGF-I levels associated with extended longevity in multiple model systems. The goal of this research is not gene therapy-we have no idea of what genes to change, how to change them, or what harm such changes might do-but instead to use insights from the cell biology and endocrinology of genetically long-lived mice and other species to help develop drugs that manipulate aging and thus postpone the many diseases and disabilities that are typically troublesome in old age. The complete conquest of cancer or heart disease would each lead to an increase of a mere approximately 3% in mean life span in humans, i.e. about a tenth of what can be accomplished, today, in laboratory animals of delayed aging. In this context the paltry commitment to research in biological gerontology (six cents per $100 of NIH funding, for example) seems worth reconsideration.
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PMID:Genetic approaches to the study of aging. 1613 53

Growth hormone (GH)-cell adenomas are benign pituitary tumors which present with chronic high GH output. Hereditary GH-cell adenomas are rare and include MEN I, McCune Albright Syndrome, Carney complex and familial acromegaly. Most of the tumors causing acromegaly are sporadic. Acromegaly is a disfiguring and disabling disease and, if untreated, life expectancy is reduced by a decade. Elevated GH levels, hypertension and heart disease are major negative survival determinants in these patients. Current treatments for acromegaly attempt to control the disease by reducing growth hormone secretion from the tumor either by surgery, radiotherapy or medical therapy. The choice of therapy depends on age, general health, the severity and complications of the disease and dangers associated with each treatment. Assessment of disease activity in patients with acromegaly following treatment is a problem because no sensitive clinical parameters are available and there is no well-defined clinical endpoint that defines cure. Cure in acromegaly has been defined therefore as normalization of biochemical parameters. A consensus publication recommended biochemical cure be considered as nadir GH of less than 1 microm g/L after OGTT and a normal circulating IGF-I. In optimizing the control of acromegaly new therapeutic strategies are evolving (growth hormone receptor antagonist - pegvisomant, potent dopamine agonists, universal somatostatin receptor ligands, chimeric molecules). The aim of the evolving therapeutic strategies is to produce a normal life expectancy in patients with acromegaly.
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PMID:Acromegaly - evolving strategies. 1644 81

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

The aim of this longitudinal study was to evaluate the echocardiographic outcome of acromegalic heart disease in patients undergoing different therapeutic approaches, in order to investigate whether SSA could provide therapeutic advantages as compared with neurosurgery. In total of 36, consecutive patients undergoing SSA treatment after neurosurgery were enrolled in this study (Gr.Surg.-SSA). After 12 months of treatment, 21 patients had a controlled disease, while the remaining 15 patients displayed uncontrolled disease. Twelve acromegalic patients who did not undergo SSA treatment due to controlled disease after neurosurgery were enrolled as control group (Gr.Surg). The echocardiographic-Doppler study was performed before neurosurgery and after 12-months of follow-up. After follow-up, a significant reduction in serum GH and IGF-I values, Left Ventricular Mass index (LVMi) and LVH rate with an improvement in diastolic function was observed in both groups of patients. We found a significant reduction of LVMi either in patients with controlled disease or in those with poorly controlled disease undergoing SSA treatment. Diastolic function and of LVH percentage improved in all groups, but significantly so only in controlled patients, no significant difference in any echocardiographic parameters and in the prevalence of the LVH rate were observed between the three groups of patients at the end of follow-up. Therefore, our data appear to show that for echographic parameters medical treatment additive beneficial effects is compared to neurosurgery alone. SSA also appears to contribute to the improvement of acromegalic cardiomyopathy also in patients who did not achieve biochemical control of the disease.
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PMID:The long-term cardiovascular outcome of different GH-lowering treatments in acromegaly. 1798 89


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