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statins and calcium homeostasis

Gaurav Taneja, Akash Sud, Narayan Pendse, Bishnu Panigrahi, Ashish Kumar, Arun K Sharma
The endothelium is a thin innermost layer of flat cells which release various mediators including endothelin-1 (ET-1), prostanoids, von Willebrand factor (vWF) and endothelium-derived relaxing factor (EDRF; nitric oxide) to regulate vascular tone. Endothelial nitric oxide synthase (eNOS) is a key enzyme that generates nitric oxide (NO). NO maintains vascular homeostasis and cardiac functions by influencing major vascular protective properties such as anti-platelet, anti-proliferative, anti-migratory, antioxidant and anti-inflammatory action in vessels...
November 17, 2018: Cardiovascular Toxicology
Rita Kleinauskienė, Regina Jonkaitienė
Degenerative aortic stenosis (DAS) is the most frequently diagnosed heart valve disease in Europe and North America. DAS is a chronic progressive disease which resembles development of atherosclerosis. Endothelial dysfunction, lipid infiltration, calcification and ossification are evidenced in both diseases. The same risk factors such as older age, male sex, smoking, and elevated levels of lipids are identified. The effect of smoking, visceral obesity, metabolic syndrome, hypercholesterolemia, low-density lipoprotein, high-density lipoprotein, lipoprotein(a), adiponectin and apolipoprotein(a) on development of DAS are being studied...
April 25, 2018: Medicina
Hamid Mollazadeh, Stephen L Atkin, Alexandra E Butler, Massimiliano Ruscica, Cesare R Sirtori, Amirhossein Sahebkar
The endoplasmic reticulum (ER) is critical in protein processing and particularly in ensuring that proteins undergo their correct folding to exert their functionality. What is becoming increasingly clear is that the ER may undergo increasing stress brought about by nutrient deprivation, hypoxia, oxidized lipids, point mutations in secreted proteins, cellular differentiation or significant deviation from metabolic set points, and loss of Ca2+ homeostasis, with detrimental effects on ER-resident calcium-dependent chaperones, alone or in combination...
October 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Ravinder Sodi, Jarlath Eastwood, Muriel Caslake, Chris J Packard, Laura Denby
BACKGROUND: Small non-coding microRNAs (miR) have important regulatory roles and are used as biomarkers of disease. We investigated the relationship between lipoproteins and circulating miR-30c, evaluated how they are transported in circulation and determined whether statins altered the circulating concentration of miR-30c. METHODS: To determine the relationship between lipoproteins and circulating miR-30c, serum samples from 79 subjects recruited from a lipid clinic were evaluated...
March 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
Hans D Katzberg, Charles D Kassardjian
PURPOSE OF REVIEW: This article discusses the clinical features, pathophysiology, and management of toxic and endocrine myopathies. RECENT FINDINGS: Early detection and expeditious correction of metabolic disturbances in endocrinopathies such as Cushing syndrome, thyroid and parathyroid diseases, and acromegaly can minimize and prevent neurologic complications including myopathy. Recently proposed mechanisms of injury in patients with critical illness myopathy include inhibition of protein synthesis, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, oxidative stress, and disruption of intramuscular calcium homeostasis, which can cause a myosin-loss myopathy...
December 2016: Continuum: Lifelong Learning in Neurology
Misbahuddin M Rafeeq, Farida Ahmad, Syed Z Rahman, Sheelu S Siddiqi, Shazi Shakil
AIM: Statins treat dyslipidemia associated with metabolic syndrome. Genetic factors contribute to variable response. Sterol regulatory element-binding factors cleavage-activating protein (SCAP) pathway regulates lipid homeostasis, so effect of SNP in SCAP gene on rosuvastatin response was studied. MATERIALS & METHODS: Metabolic syndrome patients with low-density lipoprotein-cholesterol ≥130 mg/dl, were prescribed rosuvastatin 5 mg for 3 months. Lipids were measured initially and finally, and genotyping done...
December 2016: Pharmacogenomics
Adrian Szobi, Martin Lichy, Slavka Carnicka, Dezider Pancza, Pavel Svec, Tana Ravingerova, Adriana Adameova
BACKGROUND: It is known that statins possess beneficial cardioprotective effects irrespective of lipidlowering action and that cardiac injury due ischemia/reperfusion is associated with Ca2+ dysregulation resulting in contractile dysfunction. OBJECTIVE: With this background, we tested a hypothesis that simvastatin influences signaling of Ca2+/calmodulindependent protein kinase IIδ (CaMKIIδ), a protein kinase regulating both Ca2+ homeostasis and thick filament function, and thereby might underlie the mitigation of ischemia/reperfusion (I/R)-induced cardiac dysfunction...
2016: Current Pharmaceutical Design
Ghazala Yasmeen, Manohar Lal Dawani, Tabassum Mahboob
Ischemic nephropathy is an emerging cause of end stage renal disease, associated with many co-morbidities especially cardiovascular disease risk and derangement in calcium-phosphorus homeostasis resulting in hyperphosphatemia, influencing bones, a characteristic of advancing chronic kidney disease. The management of elevated serum phosphorus has been a challenge in this patient population with compromised kidney performance, as available phosphorus lowering agents possess many undesirable hazardous secondary effects and/or are very expensive...
2015: EXCLI Journal
Robert Krysiak, Wojciech Gilowski, Bogusław Okopień
BACKGROUND: By reducing LDL cholesterol levels, statins may decrease androgen production. This study was aimed at investigating whether testosterone treatment has an impact on cardiometabolic risk factors in statin-treated men with late-onset hypogonadism (LOH). METHODS: The study included 31 men with LOH who had been treated for at least 6 months with atorvastatin (20-40mg daily). On the basis of patient preference, atorvastatin-treated patients were divided into two matched groups of patients: receiving intramuscular testosterone enanthate (100mg weekly, n=16) and not treated with this hormone (n=15)...
February 2016: Pharmacological Reports: PR
Marcello Rattazzi, Elisabetta Faggin, Roberta Buso, Roberto Di Virgilio, Massimo Puato, Mario Plebani, Martina Zaninotto, Tiziana Palmosi, Elisa Bertacco, Gian Paolo Fadini, Paolo Pauletto
AIM: Circulating osteoprogenitors and receptor activator of nuclear factor kappa-B ligand (RANKL) expression in immune cells have been implicated in the pathogenesis of osteoporosis and vascular calcification. The role played by statin therapy in the bone-vascular axis is unknown. METHODS: Twenty naïve postmenopausal osteoporotic hypercholesterolemic women were treated with Atorvastatin 40 mg/day for 3 months. Gene expression analysis was performed to assess modification in osteoprotegerin (OPG)/RANK/RANKL expression in isolated T cells and monocytes...
February 2016: Cardiovascular Therapeutics
Frédéric Capel, Gwladys Chabrier, Elodie Pitois, Jean-Paul Rigaudière, Servane Le Plenier, Christine Durand, Chrystèle Jouve, Jean-Pascal de Bandt, Luc Cynober, Christophe Moinard, Béatrice Morio
BACKGROUND AND PURPOSE: NO is a crucial regulator of energy and lipid metabolism, whose homeostasis is compromised during obesity. Combination of citrulline and atorvastatin potentiated NO production in vitro. Here we have assessed the effects of this combination in mice with diet-induced obesity (DIO). EXPERIMENTAL APPROACH: C57BL/6J male mice were given a standard diet (control) or a high fat-high sucrose diet (DIO) for 8 weeks. DIO mice were then treated with DIO alone, DIO with citrulline, DIO with atorvastatin or DIO with citrulline and atorvastatin (DIOcit-stat) for 3 weeks...
October 2015: British Journal of Pharmacology
Olga Barbarash, Olga Gruzdeva, Evgenya Uchasova, Ekaterina Belik, Yulia Dyleva, Victoria Karetnikova
BACKGROUND: Dyslipidemia is a key factor determining the development of both myocardial infarction (MI) and its subsequent complications. Dyslipidemia is associated with endothelial dysfunction, activation of inflammation, thrombogenesis, and formation of insulin resistance. Statin therapy is thought to be effective for primary and secondary prevention of complications associated with atherosclerosis. METHODS: This study examined 210 patients with Segment elevated MI (ST elevated MI) who were treated with atorvastatin from the first 24 hours after MI...
2015: Drug Design, Development and Therapy
Gabriella Di Giovine, Monica Verdoia, Lucia Barbieri, Alon Schaffer, Gianluca Aimaretti, Giorgio Bellomo, Paolo Marino, Harry Suryapranata, Fabiola Sinigaglia, Giuseppe De Luca
BACKGROUND: Previous reports have suggested an association between elevated fibrinogen and CAD. Few studies have so far investigated the impact of diabetes on fibrinogen levels and its association with coronary artery disease (CAD) and platelet reactivity in diabetic patients that are therefore the aims of the current study. METHODS: We measured fibrinogen in 3280 consecutive patients undergoing coronary angiography. Samples were collected at admission for fibrinogen levels assessment...
September 2015: Diabetes Research and Clinical Practice
Robert Krysiak, Wojciech Gilowski, Witold Szkrobka, Bogusław Okopien
AIMS: Hyperprolactinemia is often associated with hyperinsulinemia, insulin resistance, atherogenic dyslipidemia, and subclinical atherosclerosis. Dopamine agonists were found to reduce the prevalence of metabolic syndrome and cardiometabolic risk. The aim of this study was to compare the effect of statin therapy on cardiovascular risk factors between patients treated with a dopamine agonist and patients treated with metformin. METHODS: The study included two age-, weight-, lipid-, and prolactin level-matched groups of premenopausal women with hypecholesterolemia and a history of hyperprolactinemia: patients treated with bromocriptine (5...
October 2015: Cardiovascular Therapeutics
Akihiro Nakagomi, Toshiyuki Shibui, Keiichi Kohashi, Munenori Kosugi, Yoshiki Kusama, Hirotsugu Atarashi, Wataru Shimizu
AIMS: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have multiple pleiotropic effects, such as anti-inflammatory and vascular endothelium protection, that are independent of their low-density-lipoprotein (LDL) cholesterol lowering effects. However, whether different statins exert diverse effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis [as indicated by the intima-media thickness (CIMT)] in patients with dyslipidemia remains unclear...
2015: Journal of Atherosclerosis and Thrombosis
J Vincze, Á Jenes, M Füzi, J Almássy, R Németh, G Szigeti, B Dienes, Z Gaál, P Szentesi, I Jóna, P Kertai, G Paragh, L Csernoch
Myalgia and muscle weakness may appreciably contribute to the poor adherence to statin therapy. Although the pathomechanism of statin-induced myopathy is not completely understood, changes in calcium homeostasis and reduced coenzyme Q10 levels are hypothesized to play important roles. In our experiments, fluvastatin and/or coenzyme Q10 was administered chronically to normocholesterolaemic or hypercholaestherolaemic rats, and the modifications of the calcium homeostasis and the strength of their muscles were investigated...
June 2015: Journal of Muscle Research and Cell Motility
Robert Krysiak, Beata Kowalska, Witold Żmuda, Bogusław Okopień
BACKGROUND: Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. METHODS: The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe...
April 2015: Pharmacological Reports: PR
R Krysiak, W Gilowski, B Okopien
BACKGROUND: The presence of hypothyroidism seems to be associated with increased cardiovascular risk. No previous study compared circulating levels of plasma lipids and other cardiovascular risk factors in statin-treated patients with different thyroid function states. METHODS: We studied 15 women with untreated subclinical hypothyroidism (group A), 16 women with treated hypothyroidism (group B) and 17 women with normal thyroid function (group C) who, because of coexistent hypercholesterolemia, were treated with atorvastatin...
March 2015: Experimental and Clinical Endocrinology & Diabetes
Dong-Bo Li, Hong-Wei Xu, Guo-Jie Yang, Jun-Min Yang, He Fang, Jun-Yan Tang
The effects of long-term rosuvastatin treatment on the regulation of cytochrome P450 (CYP) 4A1 expression and vascular homeostasis of spontaneously hypertensive rat (SHR) are still unknown. In this study SHRs were randomly divided into three groups (n=10 per group): SHR group, H-Rv group (rosuvastatin 2.5 mg·kg(-1)·d(-1)), L-Rv group (rosuvastatin 0.5 mg·kg(-1)·d(-1)), and 10 male Wistar-Kyoto (WKY) rats in the control group (WKY group). All rats were treated with rosuvastatin for 12 weeks. The systolic blood pressure (SBP), left ventricle weight index (LVWI) and plasma lipids were measured during or after treatment...
March 2015: Microvascular Research
Zidong Donna Fu, Julia Yue Cui, Curtis D Klaassen
Statins are effective cholesterol-lowering drugs to treat CVDs. Bile acids (BAs), the end products of cholesterol metabolism in the liver, are important nutrient and energy regulators. The present study aims to investigate how statins affect BA homeostasis in the enterohepatic circulation. Male C57BL/6 mice were treated with atorvastatin (100 mg/kg/day po) for 1 week, followed by BA profiling by ultra-performance LC-MS/MS. Atorvastatin decreased BA pool size, mainly due to less BA in the intestine. Surprisingly, atorvastatin did not alter total BAs in the serum or liver...
December 2014: Journal of Lipid Research
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