Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The natriuretic peptide (NP) system is composed of 3 distinct peptides (atrial natriuretic peptide or ANP, B-type natriuretic peptide or BNP, and C-type natriuretic peptide or CNP) and 3 receptors (natriuretic peptide receptor-A or NPR-A or particulate guanynyl cyclase-A natriuretic peptide receptor-B or NPR-B or particulate guanynyl cyclase-B, and natriuretic peptide receptor-C or NPR-C or clearance receptor). ANP and BNP function as defense mechanisms against ventricular stress and the deleterious effects of volume and pressure overload on the heart. Although the role of NPs in cardiovascular homeostasis has been extensively studied and well established, much remains uncertain about the signaling pathways in pathological states like heart failure, a state of impaired natriuretic peptide function. Elevated levels of ANP and BNP in heart failure correlate with disease severity and have a prognostic value. Synthetic ANP and BNP have been studied for their therapeutic role in hypertension and heart failure, and promising trials are under way. In recent years, the expression of ANP and BNP in human adipocytes has come to light. Through their role in promotion of adipocyte browning, lipolysis, lipid oxidation, and modulation of adipokine secretion, they have emerged as key regulators of energy consumption and metabolism. NPR-A signaling in skeletal muscles and adipocytes is emerging as pivotal to the maintenance of long-term insulin sensitivity, which is disrupted in obesity and reduced glucose-tolerance states. Genetic variants in the genes encoding for ANP and BNP have been associated with a favorable cardiometabolic profile. In this review, we discuss several pathways that have been proposed to explain the role of NPs as endocrine networkers. There is much to be explored about the therapeutic role of NPs in improving metabolic milieu.
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PMID:The Importance of Natriuretic Peptides in Cardiometabolic Diseases. 3253 42

The adipocyte-derived adipokine leptin exerts pleiotropic effects, which are essential for the regulation of energy balance and cell metabolism, for controlling inflammatory and immune responses, and for the maintenance of homeostasis of the cardiovascular system. Leptin resistance in obese or type 2 diabetes mellitus (T2DM) patients is defined as a decrease in tissue response to leptin. In the cardiovascular system, leptin resistance exhibits the adverse effect on the heart's response to stress conditions and promoting cardiac remodeling due to impaired cardiac metabolism, increased fibrosis, vascular dysfunction, and enhanced inflammation. Leptin resistance or leptin signaling deficiency results in the risk increase of cardiac dysfunction and heart failure, which is a leading cause of obesity- and T2DM-related morbidity and mortality. Animal studies using leptin- and leptin receptor- (Lepr) deficient rodents have provided many useful insights into the underlying molecular and pathophysiological mechanisms of obese- and T2DM-associated metabolic and cardiovascular diseases. However, none of the animal models used so far can fully recapitulate the phenotypes of patients with obese or T2DM. Therefore, the role of leptin in the human cardiovascular system, and whether leptin affects cardiac function directly or acts through a leptin-regulated neurohumoral pathway, remain elusive. As the prevalence of obesity and diabetes is continuously increasing, strategies are needed to develop and apply human cell-based models to better understand the precise role of leptin directly in different cardiac cell types and to overcome the existing translational barriers. The purpose of this review is to discuss the mechanisms associated with leptin signaling deficiency or leptin resistance in the development of metabolic and cardiovascular diseases. We analyzed and comprehensively addressed substantial findings in pathophysiological mechanisms in commonly used leptin- or Lepr-deficient rodent models and highlighted the differences between rodents and humans. This may open up new strategies to develop directly and reliably applicable models, which resemble the human pathophysiology in order to advance health care management of obesity- and T2DM-related cardiovascular complications.
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PMID:Role of Leptin in Cardiovascular Diseases. 3265 92

Neuregulins (NRGs) are protein ligands that act through ErbB receptor tyrosine kinases to regulate tissue morphogenesis, plasticity, and adaptive responses to physiologic needs in multiple tissues, including the heart and circulatory system. The role of NRG/ErbB signaling in cardiovascular biology, and how it responds to physiologic and pathologic stresses is a rapidly evolving field. While initial concepts focused on the role that NRG may play in regulating cardiac myocyte responses, including cell survival, growth, adaptation to stress, and proliferation, emerging data support a broader role for NRGs in the regulation of metabolism, inflammation, and fibrosis in response to injury. The constellation of effects modulated by NRGs may account for the findings that two distinct forms of recombinant NRG-1 have beneficial effects on cardiac function in humans with systolic heart failure. NRG-4 has recently emerged as an adipokine with similar potential to regulate cardiovascular responses to inflammation and injury. Beyond systolic heart failure, NRGs appear to have beneficial effects in diastolic heart failure, prevention of atherosclerosis, preventing adverse effects on diabetes on the heart and vasculature, including atherosclerosis, as well as the cardiac dysfunction associated with sepsis. Collectively, this literature supports the further examination of how this developmentally critical signaling system functions and how it might be leveraged to treat cardiovascular disease.
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PMID:Neuregulins: protective and reparative growth factors in multiple forms of cardiovascular disease. 3306 22


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