Cardiolipin metabolism and the role it plays in heart failure and mitochondrial supercomplex formation.
Authors: Mejia EM, Cole LK, Hatch GM Abstract Cardiolipin is a major membrane phospholipid in the mitochondria and is essential for cellular energy metabolism mediated through mitochondrial oxidative phosphorylation. Recent studies indicate that it plays a diverse role in cellular metabolism. Eukaryotic cardiolipin is synthesized de novo from phosphatidic acid via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway and is deacylated to monolysocardiolipin in order for it to be remodelled into the form that is observed in mitochondrial membranes. This resynthesis of deacylated cardiolipin from monolysocardiol...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Endothelial cell regulation of cardiac metabolism following diabetes.
Authors: Wang F, Zhang D, Wan A, Rodrigues B Abstract The earliest change that occurs in the diabetic heart is reduced glucose consumption, with a switch to utilization of fatty acids (FA) predominantly as an energy resource. Although this adaptation might be beneficial in the short-term, over a protracted duration, it is potentially catastrophic given the malicious effects produced by high FA in cardiomyocytes. In this review, we describe how the endothelial cell (EC), a "first-responder" to hyperglycemia, communicates with the underlying cardiomyocyte. As this cross-talk is expected to facilitate increa...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Caveolin-1 and ATP binding cassette transporter A1 and G1-mediated cholesterol efflux.
Authors: Wang F, Gu HM, Zhang DW Abstract Atherosclerosis is one major cause of cardiovascular diseases, the leading cause of death in industrialized countries. Reverse cholesterol transport (RCT) is thought to be one primary pathway to protect against atherosclerosis. The first and rate-limiting step of RCT is ATP-binding cassette transport A1 (ABCA1) and ABCG1-mediated cholesterol efflux from the cells. Recently, caveolin-1 (CAV1), a scaffolding protein that organizes and concentrates certain caveolin-interacting signaling molecules and receptors within caveolae membranes, has been shown to regulate ABCA1 and ABC...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Transcriptional control of collagen I gene expression.
Authors: Roche P, Czubryt MP Abstract Cardiac fibrosis is the pathological remodeling of the extracellular matrix (ECM) in response to stresses such as pressure overload or injury. While initially adaptive, myocardial remodeling and subsequent fibrosis causes increased wall stiffness, arrhythmias, cardiac dysfunction, and eventually heart failure. Though the disease processes and origins may differ, excess deposition of fibrillar collagens type I and III characterizes fibrosis in the heart, lungs, kidneys, liver, and skin. Under normal physiological conditions, high tensile strength collagen fibers maintain cardiac...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Histone methylation and transcriptional regulation in cardiovascular disease.
Authors: Xu Y, Fang F Abstract Cardiovascular disease (CVD) represents a major health risk to the global population. In disease settings, cells that constitute the vasculature undergo profound changes both morphologically and functionally paralleling alterations in gene expression profile. At the transcriptional level, gene expression is steered by the epigenetic machinery including DNA methyltransferases, histone variants, non-coding regulatory RNAs, chromatin remodeling complexes, and histone modifying enzymes. The N-terminal tails of histones, primarily histones H3 and H4, are post-translationally modified creat...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

The cardiorenal syndrome: pathophysiologic crosstalk, outcomes, and treatment targets.
Authors: Cohen L Abstract The development of simultaneous decompensation in cardiac and renal function is a common phenomenon in patients with congestive heart failure. Termed the cardiorenal syndrome (CRS), this joint deterioration in cardiac output and renal filtration is the result of a complex interplay of hemodynamic and neurohormonal factors. Recently, endothelial dysfunction, inflammation and uremia have been recognized as contributors to the crosstalk responsible for the development of CRS. Management strategies for the treatment of CRS involve correction of hemodynamic derangements and regulation of neuroh...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

NOAC in acute coronary syndrome and AF?
Authors: Niespialowska-Steuden M, Collins P, Costopoulos C, Gorog DA Abstract Cardiovascular disease remains a major cause of morbidity and mortality in developed countries. New treatments, in the form of novel oral anticoagulants (NOAC) that reduce thrombotic risk are now available for patients with atrial fibrillation (AF) or acute coronary syndrome (ACS). Warfarin has been the cornerstone of thromboprophylaxis in patients with AF, but treatment is cumbersome, inconvenient and often unreliable, with fluctuating time in therapeutic range. Thrombotic events also continue to occur in a significant number of ACS pati...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Alogliptin; a review of a new dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes mellitus.
Authors: Said S, Nwosu AC, Mukherjee D, Hernandez GT Abstract Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are effective and safe oral incretin-based antihyperglycemic drugs. In preclinical studies, DPP-4 inhibitors have demonstrated cardiovascular benefits, independent of glycemic control, in patients with type-2 diabetes mellitus. Since 2005, various DPP-4 inhibitors (sitagliptin, linagliptin and saxagliptin) have been clinically available in the United States. Since 2013, alogliptin is the 4(th) approved DPP-4 inhibitor available on the market. Studies have shown that alogliptinis non-inferior to compara...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

A review of dietary influences on cardiovascular health: part 2: dietary patterns.
Authors: Stradling C, Hamid M, Taheri S, Thomas GN Abstract Dietary recommendations are key to cardiovascular disease (CVD) management. The underpinning evidence is generally based on data generated from single nutrient or food types. However, food is not consumed in such a manner, and components may interact synergistically or antagonistically depending on the dietary composition. Analyses of dietary patterns have attempted to address these important issues. The aim of this review is to present the current evidence on three major dietary patterns and their relationship with CVD. The most widely reported is the Med...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Editorial: renal endothelial dysfunction: evolving concepts and perspectives.
Authors: Guerrot D, Bellien J PMID: 25088123 [PubMed - in process] (Source: Cardiovascular and Hematological Disorders Drug Targets)
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Renal endothelial dysfunction in acute kidney ischemia reperfusion injury.
Authors: Basile DP, Yoder MC Abstract Acute kidney injury is associated with alterations in vascular tone that contribute to an overall reduction in GFR. Studies in animal models indicate that ischemia triggers alterations in endothelial function that contribute significantly to the overall degree and severity of a kidney injury. Putative mediators of vasoconstriction that may contribute to the initial loss of renal blood flow and GFR are highlighted. In addition, there is discussion of how intrinsic damage to the endothelium impairs homeostatic responses in vascular tone as well as promotes leukocyte adhesion and ...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Atrial fibrillation - new frontiers in anticoagulation.
Authors: Thomas R, Page PL, Mitchell AR Abstract Stroke is the most feared complication of atrial fibrillation but for over fifty years there has been no simple, effective preventative alternative to warfarin. The development of new risk algorithms such as CHADSVASC has resulted in more patients being recommended anticoagulation therapy. Fixed dose oral anticoagulation is a landmark in drug development for atrial fibrillation. The differences between the drugs are discussed and the trial data examined. As we enter this new frontier of therapy, there is no doubt that these drugs will transform the delivery of antico...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Novel anticoagulants vs warfarin for stroke prevention in atrial fibrillation.
Authors: Turagam MK, Velagapudi P, Bongu NR, Kocheril AG Abstract Warfarin has remained the mainstay of stroke prevention in atrial fibrillation for the past 60 years. Recently, two new groups of novel oral anticoagulants- direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) have shown promising results in well conducted clinical trials in terms of efficacy, safety and convenience of usage. However, in real world practice these novel agents come with their share of side effects and drawbacks which the prescribing physician must be aware about. In this review we discuss ...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Phospholipid transfer protein in diabetes, metabolic syndrome and obesity.
Authors: Qin S, Song G, Yu Y Abstract It has been reported that phospholipid transfer protein (PLTP) is an independent risk factor for human coronary artery disease. And metabolic tissues are important contributors to the systemic pools of PLTP protein. Consistently, PLTP mass and activity have been found to be elevated in the plasma of type 2 diabetes mellitus (T2DM) and obese patients. In this review, we summarized the recent progresses made in the PLTP research field and focused on the complexity of the implication of PLTP in obesity, insulin resistance and T2DM. PMID: 25107452 [PubMed - in process] (Source...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Interaction between thienopyridines and proton pump inhibitors.
Authors: Yildiz BS, Yildiz M, Akin I Abstract Adenosin diphospat (ADP) plays a crucial role in thrombus formation. Therefore its inhibition can control excess platelet generation to prevent cardiovascular events in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). One of ADP's target receptors, P2Y12 has a limited tissue distribution and is therefore an attractive pharmacological target. Thienopyridines are class of drugs that specifically and irreversibly inhibit the P2Y12 receptor. Three generations exist and in most patients, they are administered in combination ...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Triple antiplatelet therapy after PCI--should or could it be done?
Authors: Yildiz BS, Yildiz M, Aydin E, Akin I Abstract In case of coronary stenting in patients taking long-term oral anticoagulants (OAC), addition of both aspirin and clopidogrel in the drug regimen (so-called triple antiplatelet therapy) is recommended. However such triple therapy increases the risk of serious bleeding events. Comparative data on the efficacy and safety of the triple therapy versus therapy with a single antiplatelet agent and oral anticoagulants in case of coronary stenting are very rare. Most studies show a decreased stroke and myocardial infarction risk, but an increased risk of bleeding event...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Stent thrombosis--mythy and facts.
Authors: Yildiz M, Yildiz BS, Aydin E, Akin I Abstract Stent thrombosis is a serious complication in stent era. It can be presented as death, cardiogenic shock or a large non-fatal myocardial infarction, usually with ST elevation. Risks of stent thrombosis, stent thrombosis incidence and predictors are controversial issues due to sparse and controversial data. But all attending physicians should have knowledge of the risk of stent thrombosis, predisposing and protective factors before and after the intervention. This issue is discussed in detail in this review. PMID: 25174712 [PubMed - in process] (Source: Car...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Recent developments in antiplatelet therapy after percutaneus coronary intervention.
Authors: Yildiz M, Yildiz BS, Gursoy MO, Akin I Abstract Antiplatelet therapy plays an important role in the treatment of patients suffering from acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) in order to prevent atherothrombotic events and restenosis or ischemic reocclusion, respectively. Moreover, stent implantation is often performed along with PCI to ensure that the arteries remain open. However, stent thrombosis ST is a possible complication which can occur up to about one year after the procedure. Therefore, it is standard to treat patients with a dual antiplatelet regime...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Recent developments in drug-eluting coronary stents.
Authors: Yildiz M, Yildiz BS, Gursoy MO, Akin I Abstract The interventional treatment of coronary artery disease was introduced in 1970`s by Andreas Grüntzig. The initial treatment strategy with plain old balloon angioplasty (POBA) was associated with high restenosis rates. The introduction of coronary stents, especially drug-eluting stents (DES) in 2002 has improved the results by lowering the rate of in-stent restenosis from 20-40% in the era of bare-metal stent (BMS) to 6-8%. However, in 2006 with the observation of late stent thrombosis the reputations of DES have decreased. However, improvements in stent ...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Drug-eluting stents and concomitant treatment.
Authors: Akin I PMID: 25316406 [PubMed - in process] (Source: Cardiovascular and Hematological Disorders Drug Targets)
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Editorial (thematic issue: current topics in sepsis).
Authors: Shimaoka M PMID: 25567332 [PubMed - in process] (Source: Cardiovascular and Hematological Disorders Drug Targets)
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Involvement of hypoxia-inducible factors in the dysregulation of oxygen homeostasis in sepsis.
Authors: Hirota K Abstract Sepsis is a state of infection with serious systemic manifestations, and if severe enough, can be associated with multiple organ dysfunction and systemic hypotension, which can cause tissues to be hypoxic. Inflammation, as part of the multifaceted biological response to injurious stimuli, such as pathogens or damaged tissues and cells, underlies these biological processes. Prolonged and persistent inflammation, also known as chronic inflammation, results in progressive alteration in the various types of cells at the site of inflammation and is characterized by the simultaneous destruction...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Oral inflammation and bacteremia: implications for chronic and acute systemic diseases involving major organs.
This article presents a review of the possible pathologic consequences of bacteremia originating in the oral cavity and points out the most commonly affected organs as well as preventive and treatment measures. At the present time, plaque control by subjects and/or dental professionals is one of the most effective means to prevent the onset and progression of oral bacteremia-induced systemic diseases. PMID: 25567334 [PubMed - in process] (Source: Cardiovascular and Hematological Disorders Drug Targets)
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Sepsis pathophysiology and anesthetic consideration.
Authors: Yuki K, Murakami N Abstract Sepsis remains to be a significant health care issue associated with high mortality and healthcare cost, despite the extensive effort to better understand the pathophysiology of the sepsis. Recently updated clinical guideline for severe sepsis and septic shock, "Surviving Sepsis Campaign 2012", emphasizes the importance of early goal-directed therapy, which can be implemented in intraoperative management of sepsis patients. Herein, we review the updates of current guideline and discuss its application to anesthesic management. Furthermore, we review the recent advance ...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Extracorporeal lung assist for sepsis and acute respiratory distress syndrome.
Authors: Iwashita Y, Imai H Abstract Acute respiratory distress syndrome (ARDS) is one of the major causes of ICU deaths. Extracorporeal lung assist (ECLA) has been used as a rescue therapy for most severe form of ARDS. However, its survival benefit had not been shown until CESAR trial in 2009. This has been because the concept of lung protective ventilation strategy had not yet known. Since CESAR trial, the clinical application of ECLA for ARDS as a method to achieve lung rest has wide spread. The effectiveness is further appreciated during the 2009 H1N1 influenza pandemic. The succeeded countries achieved buildin...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Mechanical Ventilation for ARDS Patients - For a Better Understanding of the 2012 Surviving Sepsis Campaign Guidelines.
Authors: Takeuchi M, Tachibana K Abstract The mortality rate among patients suffering acute respiratory distress syndrome (ARDS) remains high despite implementation at clinical centers of the lung protective ventilatory strategies recommended by the International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. This suggests that such strategies are still sub-optimal for some ARDS patients. For these patients, tailored use of ventilator settings should be considered, including: further reduction of tidal volumes, administration of neuromuscular blocking agents if the patient's spontaneous breathin...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Neutrophil migration under normal and sepsis conditions.
Authors: Lerman YV, Kim M Abstract Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also p...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Neuroinflammation in sepsis: sepsis associated delirium.
We present in detail the pathophysiology with regards to blood-brain-barrier breakdown, cytokine activation and neurotransmitter deregulation. Treatment and prognosis for SAD are also briefly discussed. SAD is the most common form of delirium acquired in the ICU (Intensive Care Unit), and is described in about 50% of septic patients. Clinical features include altered level of consciousness, reduced attention, change in cognition and perceptual disturbances. Symptoms can reversible, but prolonged deficits can be observed in older patients. Pathophysiology of SAD is poorly understood, but involves microvascular, metabolic an...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research

Changes of Expression of the Protein C Pathway Components in LPSInduced Endotoxemia-Implication for Sepsis.
Authors: Hayashi T, Suzuki K Abstract The process of blood coagulation is mediated by activation of a series of serine-protease zymogens. The protein C (PC) anticoagulant pathway, one of the important pathways related to physiological thrombosis formation, includes PC, thrombomodulin (TM), endothelial PC receptor (EPCR), protein S (PS) and C4b-binding protein (C4BP). TM, mainly present in endothelial cells, is a cofactor for thrombin-catalyzed activation of PC, and the resulting activated PC (aPC) inactivates the blood coagulation cofactors factor Va and factor VIIIa in the presence of PS. PS, mainly synthesized in...
Source: Cardiovascular and Hematological Disorders Drug Targets - June 4, 2015 Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research