Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congestive heart failure is a multiple aetiology, high prevalence, poor prognosis cardiovascular disorder. Medical treatment of dilated cardiomyopathy is aimed at alleviating the symptoms of heart failure. Diuretics, ACE inhibitors and very recently, beta-blockers have been shown to have favourable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The roles of GH and IGF-1 as modulators of myocardial structure and function are well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, whereas IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases and, in addition, an impaired cardiac efficiency is observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by haemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is caused by ventricular dilatation with abnormal wall thickening, which leads to impaired cardiac performance; therefore, based on the evidence available for GH we would expect beneficial effects from the use of GH in these patients. Several papers highlight the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small nonblind studies, both short and long term GH treatment have demonstrated beneficial effects in patients with heart failure secondary to ischaemic or idiophatic cardiomyopathy. Recently, two randomised, placebo-controlled studies, did not show significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance, might be an important feature of severe heart failure and explain the different responses to GH therapy seen in different patients. Whether GH treatment will finally find a place, and with which modalities, in the treatment of heart failure remains to be established.
 ...
PMID:Role of growth hormone in chronic heart failure. Therapeutic implications. 1108 97

Induction of cardiac muscle regeneration following myocardial infarction (MI) represents a major challenge in cardiovascular therapy, as the current clinical approaches are limited in their ability to regenerate a new muscle tissue and to replace infarcted myocardium. Here, we describe the conception of two strategies based on bio-inspired materials, aimed at myocardial repair after MI. In the first strategy, alginate biomaterial was designed with affinity-binding moieties, enabling the binding of heparin-binding proteins and their controlled presentation and release. The combined features of this unique alginate hydrogel, as a temporary extracellular matrix replacement and a depot for bio-molecules such as insulin-like growth factor-1 and hepatocyte growth factor, led to improvements in cardiac structure and function, as demonstrated by the biomaterial's abilities to thicken the scar and prevent left-ventricular remodeling and dilatation. Endogenous regeneration occurring at the infarct as manifested by the enhanced angiogenesis, cardiomyocyte proliferation, and appearance of cardiac-related stem cells is likely to have contributed to this. In the second strategy, phosphatidylserine (PS)-presenting liposomes were developed to mimic apoptotic cells bodies, specifically their capability of immunomodulating activated macrophages into anti-inflammatory state. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging. The treatment promoted angiogenesis, the preservation of small scars, and prevention of ventricular dilatation and remodeling. Collectively, the two bio-inspired material-based strategies presented herein represent unique and clinical accessible approaches for myocardial infarct repair.
 ...
PMID:Bioengineering the infarcted heart by applying bio-inspired materials. 2165 74

Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models have demonstrated attenuated dilatation and improved systolic function after growth hormone administration. In addition to ameliorating wall-stress and preserving the peri-infarct myocardium, antiarrhythmic actions were also evident after such treatment, but the precise underlying mechanisms remain poorly understood. The present article summarizes the acute and chronic actions of systemic and local growth hormone administration in the post-infarction setting, placing emphasis on the electrophysiologic effects. Experimental and clinical data are reviewed, and hypotheses on potential mechanisms of action are discussed. Such information may prove useful in formulating new research questions and designing new studies that are expected to increase the translational value of growth hormone therapy after acute myocardial infarction.
 ...
PMID:Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction. 3201 45

Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this post-hoc analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants. Methods: This report is an exploratory post-hoc analysis of a phase II trial in which infants <28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers. Results: The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II-III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (n = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed. Conclusion: The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start.
 ...
PMID:Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury. 3316 63