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)

Hypertension is a leading cause of morbidity and mortality worldwide. Individuals with hypertension are at increased risk of stroke, heart disease and kidney failure. Both genetic and lifestyle factors, particularly diet, have been attributed an important role in the development of hypertension. Reducing dietary sugar and salt intake can help lower blood pressure; similarly, adequate protein intake may also attenuate hypertension. Observational, cross-sectional and longitudinal epidemiological studies, and controlled clinical trials, have documented significant inverse associations between protein intake and blood pressure. Human and animal studies have shown that specific amino acids within proteins may have antihypertensive effects. Cysteine, glutathione (a tripeptide), glutamate and arginine attenuate and prevent alterations that cause hypertension including insulin resistance, decreased nitric oxide bioavailability, altered renin angiotensin system function, increased oxidative stress and formation of advanced glycation end products. Leucine increases protein synthesis in skeletal muscle and improves insulin resistance by modulating hepatic gluconeogenesis. Taurine and tryptophan attenuate sympathetic nervous system activity. Soy protein helps lower blood pressure through its high arginine content and antioxidant activity exhibited by isoflavones. A diet containing an ample amount of protein may be a beneficial lifestyle choice for individuals with hypertension; one example is the Dietary Approaches to Stop Hypertension (DASH) diet, which is low in salt and saturated fat; includes whole grains, lean meat, poultry, fish and nuts; and is rich in vegetables, fruits and low-fat dairy products, which are good sources of antioxidant vitamins, minerals and fibre. Including an adequate supply of soy in the diet should also be encouraged.
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PMID:Antihypertensive effects of dietary protein and its mechanism. 2247 79

The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development.
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PMID:Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity. 2499 40

Trans-resveratrol has demonstrated the potential to provide both therapeutic and preventive activities against chronic diseases such as heart disease and cancer. The incorporation of trans-resveratrol into food products would allow for broader access of this bioactive compound to a larger population. However, this strategy is limited by instability of trans-resveratrol under environmental conditions and within the digestive system leading to isomerization of trans-resveratrol (bioactive form) to cis-resveratrol (bio-inactive form). Studies in the stabilization of trans-resveratrol into protein microparticles are presented. Trans-resveratrol was encapsulated using whey protein concentrate (WPC) or sodium caseinate (SC), with or without anhydrous milk fat (AMF). Binding of resveratrol and aromatic residues in protein was estimated utilizing the Stern-Volmer equation and the number of tryptophan residues. The stability of encapsulated resveratrol was evaluated after exposure to ultraviolet A (UVA) light and 3-stage in vitro digestion. After UVA light exposure, SC-based microcapsules maintained a higher trans:cis resveratrol ratio (0.63, P < 0.05) than WPC-based microcapsules (0.43) and unencapsulated resveratrol (0.49). In addition, encapsulation of resveratrol in both protein microparticles led to an increased digestive stability and bioaccessibility in comparison to unencapsulated resveratrol (47% and 23%, respectively, P < 0.05). SC-based microcapsules provided a higher digestive stability and bioaccessibility (86% and 81%; P < 0.05) compared to WPC-based microcapsules (71% and 68%). The addition of AMF to the microcapsules did not significantly change the in vitro digestion values. In conclusion, SC-based microencapsulation increased the stability of trans-resveratrol to UVA light exposure and simulated digestion conditions. This encapsulation-system-approach can be extended to other labile, bioactive polyphenols.
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PMID:Stability of Trans-Resveratrol Encapsulated in a Protein Matrix Produced Using Spray Drying to UV Light Stress and Simulated Gastro-Intestinal Digestion. 2667 8

Cardioplegic reperfusion during a long term ischemic period interrupts cardiac surgery and also increases cellular edema due to repeated solution administration. We reviewed the clinical experiences on myocardial protection of a single perfusion with histidine-tryptophan-ketoglutarate (HTK) for high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease. This retrospective study included 101 high-risk patients undergoing arterial switch operation between March 2001 and July 2012. We divided the cohort into two groups: HTK group, myocardial protection was carried out with one single perfusion with HTK solution; and St group, myocardial protection with conventional St. Thomas' crystalloid cardioplegic solution. The duration of cardiopulmonary bypass did not differ between the two groups. The mortality, morbidity, ICU stay, post-operative hospitalization time, and number of transfusions in HTK group were lower than those in St group (P<0.05). Univariate and multivariate analysis showed that HTK is a statistically significant independent predictor of decreased early mortality and morbidity (P<0.05). In conclusion, HTK solution seems to be an effective and safe alternative to St. Thomas' solution for cardioplegic reperfusion in high-risk patients with complex congenital heart disease.
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PMID:Histidine-tryptophan-ketoglutarate solution decreases mortality and morbidity in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease: an 11-year experience from a single institution. 2719 7

Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging. The first catabolic step in KP is primarily controlled by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Following this first step, the KP has two major branches, one branch is mediated by kynurenine 3-monooxygenase (KMO) and kynureninase (KYNU) and is responsible for the formation of 3-HK, 3-HAA, and quinolinic acid (QA); and another branch is controlled by kynurenine amino-transferase (KAT), which generates KA. Uncontrolled Trp catabolism has been demonstrated in distinct CVD, thus, understanding the underlying mechanisms by which regulates KP enzyme expression and activity is paramount. This review highlights the recent advances on the effect of KP enzyme expression and activity in different tissues on the pathological mechanisms of specific CVD, KP is an inflammatory sensor and modulator in the cardiovascular system, and KP catabolites act as the potential biomarkers for CVD initiation and progression. Moreover, the biochemical features of critical KP enzymes and principles of enzyme inhibitor development are briefly summarized, as well as the therapeutic potential of KP enzyme inhibitors against CVD is briefly discussed.
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PMID:Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases. 2831 92

The extracellular loop 2 (ECL2) region is the most conserved of the three ECL domains in family B G protein-coupled receptors (GPCRs) and has a fundamental role in ligand binding and activation across the receptor super-family. ECL2 is fundamental for ligand-induced activation of the calcitonin gene related peptide (CGRP) receptor, a family B GPCR implicated in migraine and heart disease. In this study we apply a comprehensive targeted non-alanine substitution analysis method and molecular modelling to the functionally important residues of ECL2 to reveal key molecular interactions. We identified an interaction network between R274/Y278/D280/W283. These amino acids had the biggest reduction in signalling following alanine substitution analysis and comprise a group of basic, acidic and aromatic residues conserved in the wider calcitonin family of class B GPCRs. This study identifies key and varied constraints at each locus, including diverse biochemical requirements for neighbouring tyrosine residues and a W283H substitution that recovered wild-type (WT) signalling, despite the strictly conserved nature of the central ECL2 tryptophan and the catastrophic effects on signalling of W283A substitution. In contrast, while the distal end of ECL2 requires strict conservation of hydrophobicity or polarity in each position, mutation of these residues never has a large effect. This approach has revealed linked networks of amino acids, consistent with structural models of ECL2 and likely to represent a shared structural framework at an important ligand-receptor interface that is present across the family B GPCRs.
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PMID:Understanding the molecular functions of the second extracellular loop (ECL2) of the calcitonin gene-related peptide (CGRP) receptor using a comprehensive mutagenesis approach. 2857 46

Cardioplegic reperfusion during a long-term ischemic period interrupts cardiac surgery and increases cellular edema due to repeated administration. The present clinical study compared the protective effects of histidine-ketoglutarate-tryptophan (HTK) solution and St. Thomas crystalloid cardioplegia. Clinical experiences of the myocardial protection induced by one single perfusion with HTK were reviewed in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease. This retrospective study included 88 high-risk patients (aortic cross-clamp time, >120 min) between March 2001 and July 2012. The cohort was divided into two groups according to the technique used. Either myocardial protection was performed with one single perfusion with HTK solution (HTK group) or with conventional St. Thomas crystalloid cardioplegia (St group). The duration of cardiopulmonary bypass did not differ between the two groups. The mortality, morbidity, intensive care unit (ICU) stay, postoperative hospitalization, and transfusions of HTK group are significantly lower than those of the St group (P<0.05). Univariate and multivariate analysis demonstrated that HTK is a statistically significant independent predictor of decreased early mortality and morbidity (P<0.05). In conclusion, the present findings suggested that HTK solution decreases mortality, morbidity, ICU stay, postoperative hospitalization, and transfusions in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease.
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PMID:Clinical comparative analysis of histidine-tryptophan-ketoglutarate solution and St. Thomas crystalloid cardioplegia: A 12-year study from a single institution. 2896 11

Obesity is a major risk factor for diabetes, heart disease and other health problems. Adipose tissue plays a central role in the development of obesity and obesity-associated diseases. Gene therapy targeting adipose tissue may provide a promising strategy for obesity treatment. However, nucleic acid delivery to adipose tissue or even cultured adipocytes is challenging due to low delivery efficacy and high toxicity of the current cationic lipid based delivery systems, or monoamphiphiles. Herein, we report using dendritic peptide bolaamphiphiles (bolas) to deliver siRNA to primary adipocytes and hepatocytes. The bola consists of two l-Lysine dendrons connected to a fluorocarbon core through disulfide linkages. The Lysine dendrons are functionalized with l-histidine and l-tryptophan to promote endosomal escape and cellular uptake. The bola exhibited over 70% knockdown of GAPDH gene in both primary adipocytes and hepatocytes. Importantly, different from Lipofectamine that significantly reduced genes involved in lipolysis, lipogenesis, fatty acid oxidation and ketogenesis, the bolas had little to no effect on these genes. These results demonstrate the bola as a promising new vector for clinical and experimental applications for delivery of siRNA to metabolic organs.
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PMID:Dendritic peptide bolaamphiphiles for siRNA delivery to primary adipocytes. 2970 1

Altered central carbon metabolism is a hallmark of many diseases including diabetes, obesity, heart disease and cancer. Identifying metabolic changes will open opportunities for better understanding aetiological processes and identifying new diagnostic, prognostic, and therapeutic targets. Comprehensive and robust analysis of primary metabolic pathways in cells, tissues and bio-fluids, remains technically challenging. We report on the development and validation of a highly reproducible and robust untargeted method using anion-exchange tandem mass spectrometry (IC-MS) that enables analysis of 431 metabolites, providing detailed coverage of central carbon metabolism. We apply the method in an untargeted, discovery-driven workflow to investigate the metabolic effects of isocitrate dehydrogenase 1 (IDH1) mutations in glioblastoma cells. IC-MS provides comprehensive coverage of central metabolic pathways revealing significant elevation of 2-hydroxyglutarate and depletion of 2-oxoglutarate. Further analysis of the data reveals depletion in additional metabolites including previously unrecognised changes in lysine and tryptophan metabolism.
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PMID:Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells. 3243 36


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