PeerJ Preprints: Cardiologyhttps://peerj.com/preprints/index.atom?journal=peerj&subject=3600Cardiology articles published in PeerJ PreprintsMelatonin combination with perindopril alleviated doxorubicin cardiac toxicity in L-NAME hypertensive rats: comparative study with perindoprilhttps://peerj.com/preprints/278632019-07-182019-07-18Takwa Mohammed Abdul SalamAmany Helmy HasaninWesam El-BaklyMona Hussein RaafatNesreen OmarAhmed El Sayed Badawy
Introduction: Doxorubicin is a highly effective anticancer agent with serious cardiotoxic effects. Hypertension is considered as a major risk factor for doxorubicin cardiotoxicity. It should be noted that about one-third of cancer patients have hypertension, and melatonin can have cardio-protective effects. The present study aimed to further investigate the possible beneficial effects of melatonin co-administration to perindopril against doxorubicin cardiotoxicity in hypertensive rats. Method: Rats were randomly assigned to naïve group and L-NAME group, which was further subdivided into untreated, doxorubicin, doxorubicin/perindopril, doxorubicin/melatonin and doxorubicin/perindopril/melatonin subgroups. Cardiac functions, CK-MB, malondialdehyde, superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and cardiac percentage area of collagen fibers were evaluated. Results: Combining melatonin with perindopril to doxorubicin produced significant decreases in left ventricular end diastolic pressure, malondialdehyde, TNF-α, and TGF-β. It resulted in significant increases in left ventricular dP/dtmax and SOD, in addition to apparent improvement in cardiac histopathology with a significant decrease in percentage area of collagen deposition compared to perindopril alone. Conclusion: Co-administration of melatonin to perindopril in hypertensive rats who received doxorubicin alleviated doxorubicin cardiac toxicity more than using perindopril alone. These effects could be explained by the reported antihypertensive, anti-inflammatory, anti-oxidant, and anti-fibrotic effects of melatonin.
Introduction: Doxorubicin is a highly effective anticancer agent with serious cardiotoxic effects. Hypertension is considered as a major risk factor for doxorubicin cardiotoxicity. It should be noted that about one-third of cancer patients have hypertension, and melatonin can have cardio-protective effects. The present study aimed to further investigate the possible beneficial effects of melatonin co-administration to perindopril against doxorubicin cardiotoxicity in hypertensive rats. Method: Rats were randomly assigned to naïve group and L-NAME group, which was further subdivided into untreated, doxorubicin, doxorubicin/perindopril, doxorubicin/melatonin and doxorubicin/perindopril/melatonin subgroups. Cardiac functions, CK-MB, malondialdehyde, superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and cardiac percentage area of collagen fibers were evaluated. Results: Combining melatonin with perindopril to doxorubicin produced significant decreases in left ventricular end diastolic pressure, malondialdehyde, TNF-α, and TGF-β. It resulted in significant increases in left ventricular dP/dtmax and SOD, in addition to apparent improvement in cardiac histopathology with a significant decrease in percentage area of collagen deposition compared to perindopril alone. Conclusion: Co-administration of melatonin to perindopril in hypertensive rats who received doxorubicin alleviated doxorubicin cardiac toxicity more than using perindopril alone. These effects could be explained by the reported antihypertensive, anti-inflammatory, anti-oxidant, and anti-fibrotic effects of melatonin.Catheter ablation vs antiarrhythmic medication in atrial fibrillationhttps://peerj.com/preprints/277692019-05-302019-05-30Eric W ManheimerMartin MayerBrian S Alper
The CABANA and CAPTAF trials report more data on the effects of catheter ablation vs. antiarrhythmic medication on quality of life for patients with atrial fibrillation than previously available systematic reviews. However, these publications do not report data for all-cause mortality and cardiac hospitalization in a form that can be integrated into recent meta-analyses.
Recent meta-analysis estimates for the effect of catheter ablation on all-cause mortality suggest a reduction in patients with comorbid heart failure with reduced ejection fraction (HFrEF) (risk ratio [RR] 0.52, 95% CI 0.33 to 0.81, n=732, 5 trials) and an unclear effect in patients without comorbid HFrEF (RR 0.88, 95% CI 0.29 to 2.61, n=710, 4 trials).
CABANA (n = 2,204) reported mortality for all patients combined (hazard ratio 0.86, 95% CI 0.65 to 1.15), and subgroup analyses by presence or absence of HFrEF would be useful to determine consistency with other trials and, if consistent, increase precision of pooled effect estimates. CAPTAF (n = 155) (which included almost exclusively patients without comorbid heart failure) did not report the mortality outcome data.
Both trials collected data on cardiac hospitalization. A recent meta-analysis suggests a reduction in cardiac hospitalization in patients with comorbid HFrEF (RR 0.63, 95% CI 0.46 to 0.87, n=632, 3 trials) and in patients without comorbid HFrEF (RR 0.32, 95% CI 0.23 to 0.45, n=629, 4 trials). Again, however, the CABANA and CAPTAF trials did not report these data in a way that would allow them to be integrated into existing meta-analyses or did not report these data at all. Reporting key clinical outcomes from these trials with subgrouping by comorbid HFrEF could provide substantially more data than the prior body of evidence and inform best current estimates for this comparison.
The CABANA and CAPTAF trials report more data on the effects of catheter ablation vs. antiarrhythmic medication on quality of life for patients with atrial fibrillation than previously available systematic reviews. However, these publications do not report data for all-cause mortality and cardiac hospitalization in a form that can be integrated into recent meta-analyses.Recent meta-analysis estimates for the effect of catheter ablation on all-cause mortality suggest a reduction in patients with comorbid heart failure with reduced ejection fraction (HFrEF) (risk ratio [RR] 0.52, 95% CI 0.33 to 0.81, n=732, 5 trials) and an unclear effect in patients without comorbid HFrEF (RR 0.88, 95% CI 0.29 to 2.61, n=710, 4 trials).CABANA (n = 2,204) reported mortality for all patients combined (hazard ratio 0.86, 95% CI 0.65 to 1.15), and subgroup analyses by presence or absence of HFrEF would be useful to determine consistency with other trials and, if consistent, increase precision of pooled effect estimates. CAPTAF (n = 155) (which included almost exclusively patients without comorbid heart failure) did not report the mortality outcome data.Both trials collected data on cardiac hospitalization. A recent meta-analysis suggests a reduction in cardiac hospitalization in patients with comorbid HFrEF (RR 0.63, 95% CI 0.46 to 0.87, n=632, 3 trials) and in patients without comorbid HFrEF (RR 0.32, 95% CI 0.23 to 0.45, n=629, 4 trials). Again, however, the CABANA and CAPTAF trials did not report these data in a way that would allow them to be integrated into existing meta-analysesor did not report these data at all. Reporting key clinical outcomes from these trials with subgrouping by comorbid HFrEF could provide substantially more data than the prior body of evidence and inform best current estimates for this comparison.Sex Matters in Health and Disease: a review of biological sex differences with an emphasis on gliomahttps://peerj.com/preprints/277162019-05-092019-05-09Susan Christine MasseyPaula WhitmireTatum E DoyleJoseph E IppolitoMaciej M MrugalaLeland S HuPeter CanollAlexander R A AndersonMelissa A WilsonSusan M FitzpatrickMargaret M McCarthyJoshua B RubinKristin R Swanson
Humans are sexually dimorphic, with sex being the most persistent difference among humans over the course of our evolutionary history. Beyond the visible sex differences that can be considered true dimorphisms, there are also sex differences at the molecular and cellular scales. The role of these biological sex differences for human health, while being increasingly recognized, have long been underappreciated and underexplored. Frequently, these differences are only recognized in sex–specific diseases, such as genitourinary diseases and cancers. However, given the evidence for sex differences in the most basic aspects of human biology, including metabolism, cellular composition, and immune activity, these differences could have consequences for the etiology and pathophysiology of a majority of diseases. It is thus essential to consider the extent to which these differences may influence the various mechanisms underlying disease processes, response to treatment, and the maintenance of health in order to better improve patient outcomes. Here we review the evidence for a broad array of biological sex differences in humans and discuss how they may relate to observed sex differences in various diseases, with an emphasis on cancer, specifically glioblastoma. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.
Humans are sexually dimorphic, with sex being the most persistent difference among humans over the course of our evolutionary history. Beyond the visible sex differences that can be considered true dimorphisms, there are also sex differences at the molecular and cellular scales. The role of these biological sex differences for human health, while being increasingly recognized, have long been underappreciated and underexplored. Frequently, these differences are only recognized in sex–specific diseases, such as genitourinary diseases and cancers. However, given the evidence for sex differences in the most basic aspects of human biology, including metabolism, cellular composition, and immune activity, these differences could have consequences for the etiology and pathophysiology of a majority of diseases. It is thus essential to consider the extent to which these differences may influence the various mechanisms underlying disease processes, response to treatment, and the maintenance of health in order to better improve patient outcomes. Here we review the evidence for a broad array of biological sex differences in humans and discuss how they may relate to observed sex differences in various diseases, with an emphasis on cancer, specifically glioblastoma. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.Sex differences in the response to angiotensin II receptor blockade in a rat model of eccentric cardiac hypertrophyhttps://peerj.com/preprints/276502019-04-122019-04-12Élisabeth Walsh-WilkinsonMarie-Claude DroletCharlie Le HouillierÈve-Marie RoyMarie ArsenaultJacques Couet
Aim of study was to evaluate the development of cardiac hypertrophy (CH) in response to left ventricle (LV) volume overload (VO) caused by chronic aortic valve regurgitation (AR) in male and female rats treated or not with angiotensin II receptor blocker (ARB), valsartan. We studied 8 groups of Wistar rats: male or female, AR or sham-operated (sham) and treated or not with valsartan (30 mg/kg/day) for 9 weeks starting one week before AR surgical induction. As expected, VO from AR resulted for both male and female rats in significant LV dilation (39% vs. 40% increase of end-diastolic LV diameter, respectively; p<0.0001) and CH (53% vs. 64% increase of heart weight, respectively; p<0.0001) compared to sham. Sex differences were observed in the LV wall thickening in response to VO. In untreated AR males, relative LV wall thickness (a ratio of wall thickness to end-diastolic diameter) was reduced compared to sham, whereas this ratio in females remained unchanged. ARB treatment did not prevent LV dilation for both male and female animals but reversed LV wall thickening in females. Systolic and diastolic functions in AR animals were altered similarly for both sexes compared to sham. ARB treatment did not improve systolic function but help normalizing diastolic parameters in female AR rats. Increased LV expression of Anp and Bnp genes was normalized by ARB treatment in AR females but not in males. Other hypertrophy gene markers (Fos, Trpc6, Klf15, Myh6 and Myh7) were not modulated by ARB treatment. The same was true for genes related to LV extracellular matrix remodeling (Col1a1, Col3a1, Fn1, Mmp2, Timp1 and Lox). In summary, ARB treatment of rats with severe AR blocked the female-specific hypertrophic response characterized by LV chamber wall thickening. LV dilation, on the other hand, was not significantly decreased by ARB treatment.
Aim of study was to evaluate the development of cardiac hypertrophy (CH) in response to left ventricle (LV) volume overload (VO) caused by chronic aortic valve regurgitation (AR) in male and female rats treated or not with angiotensin II receptor blocker (ARB), valsartan. We studied 8 groups of Wistar rats: male or female, AR or sham-operated (sham) and treated or not with valsartan (30 mg/kg/day) for 9 weeks starting one week before AR surgical induction. As expected, VO from AR resulted for both male and female rats in significant LV dilation (39% vs. 40% increase of end-diastolic LV diameter, respectively; p<0.0001) and CH (53% vs. 64% increase of heart weight, respectively; p<0.0001) compared to sham. Sex differences were observed in the LV wall thickening in response to VO. In untreated AR males, relative LV wall thickness (a ratio of wall thickness to end-diastolic diameter) was reduced compared to sham, whereas this ratio in females remained unchanged. ARB treatment did not prevent LV dilation for both male and female animals but reversed LV wall thickening in females. Systolic and diastolic functions in AR animals were altered similarly for both sexes compared to sham. ARB treatment did not improve systolic function but help normalizing diastolic parameters in female AR rats. Increased LV expression of Anp and Bnp genes was normalized by ARB treatment in AR females but not in males. Other hypertrophy gene markers (Fos, Trpc6, Klf15, Myh6 and Myh7) were not modulated by ARB treatment. The same was true for genes related to LV extracellular matrix remodeling (Col1a1, Col3a1, Fn1, Mmp2, Timp1 and Lox). In summary, ARB treatment of rats with severe AR blocked the female-specific hypertrophic response characterized by LV chamber wall thickening. LV dilation, on the other hand, was not significantly decreased by ARB treatment.Roles of pyroptosis in myocardial ischemia/reperfusion injury diseaseshttps://peerj.com/preprints/275022019-01-252019-01-25Shupeng ShiHaoran ZhangWenzhe GaoMoussa Ide NasserJie ShenMinghua YangFeng GuoLinyong XuMingyi Zhao
Ischemia-reperfusion injury (IRI) occurred when an organ lost its blood supply in a short time, and then the perfusion was restored automatically or iatrogenically, leading to a burst of reactive oxygen species (ROS) from mitochondria. It is common in the clinic, and lead to deterioration, even death, so an exploratory examination of the mechanism of ischemia-reperfusion injury is of great significance. Among the most common and fatal types of IR in myocardial tissue, myocardial IRI is one of the most fatal diseases in the modern world. The cellular and molecular mechanisms of IRI mainly include calcium overload, oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, energy metabolic disorders, neutrophil infiltration, cardiomyocyte autophagy, and apoptosis, etc. The main pathogenesis of IRI is programmed cell death, of which apoptosis is the most deeply studied processes. However, pyroptosis is a highly inflammatory form of programmed cell death (PCD), which depends on the activation of the caspase cascade and inflammatory mediators, which have been thought to be involved in the processes of IRI. Ptosis has been referred to as a pattern. PCD with apoptosis characteristics Necrosis. It’s stimulated by molecular signaling pathways similar to apoptosis, mainly including Caspase. The research progress in recent years is presented in this review. Among them, myocardial tissue and so on provide a theoretical basis for the burning organ system in I/R injury and provide theoretical practice for the clinical research of reducing ischemia-reperfusion injury.
Ischemia-reperfusion injury (IRI) occurred when an organ lost its blood supply in a short time, and then the perfusion was restored automatically or iatrogenically, leading to a burst of reactive oxygen species (ROS) from mitochondria. It is common in the clinic, and lead to deterioration, even death, so an exploratory examination of the mechanism of ischemia-reperfusion injury is of great significance. Among the most common and fatal types of IR in myocardial tissue, myocardial IRI is one of the most fatal diseases in the modern world. The cellular and molecular mechanisms of IRI mainly include calcium overload, oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, energy metabolic disorders, neutrophil infiltration, cardiomyocyte autophagy, and apoptosis, etc. The main pathogenesis of IRI is programmed cell death, of which apoptosis is the most deeply studied processes. However, pyroptosis is a highly inflammatory form of programmed cell death (PCD), which depends on the activation of the caspase cascade and inflammatory mediators, which have been thought to be involved in the processes of IRI. Ptosis has been referred to as a pattern. PCD with apoptosis characteristics Necrosis. It’s stimulated by molecular signaling pathways similar to apoptosis, mainly including Caspase. The research progress in recent years is presented in this review. Among them, myocardial tissue and so on provide a theoretical basis for the burning organ system in I/R injury and provide theoretical practice for the clinical research of reducing ischemia-reperfusion injury.Code-free bioinformatics pipeline for building biological databases used to construct cardiovascular-SNPDB: an online database for SNPs associated with cardiovascular metaboliteshttps://peerj.com/preprints/31892017-08-252017-08-25Mohammad M Tarek
Biological databases are of great importance for managing biological research data. Building databases has been a code-based process that requires integrative coding skills of different languages. Herein, we present a code-free pipeline that helps biologists to build their databases with no need for coding skills providing searchable downloadable and editable databases using Google Apps. We provided an example for an online tool including a database of SNPs associated with cardiovascular Metabolites, allowing basic features like browsing, downloading, filtering and printing. We also described a stepwise pipeline for building such an interactive database. Cardiovascular-SNPDB was made available at : https://sites.google.com/view/cvdsnpdb/browse/ .
Biological databases are of great importance for managing biological research data. Building databases has been a code-based process that requires integrative coding skills of different languages. Herein, we present a code-free pipeline that helps biologists to build their databases with no need for coding skills providing searchable downloadable and editable databases using Google Apps. We provided an example for an online tool including a database of SNPs associated with cardiovascular Metabolites, allowing basic features like browsing, downloading, filtering and printing. We also described a stepwise pipeline for building such an interactive database. Cardiovascular-SNPDB was made available at : https://sites.google.com/view/cvdsnpdb/browse/ .Species-specific pharmacology of maximakinin, an amphibian homologue of bradykinin: putative prodrug activity at the human B2 receptor and peptidase resistance in rathttps://peerj.com/preprints/26412016-12-172016-12-17Xavier Charest-MorinHélène BachelardMelissa JeanFrancois Marceau
Maximakinin (MK), an amphibian peptide possessing the C-terminal sequence of bradykinin (BK), is a BK B2 receptor (B2R) agonist eliciting prolonged signaling. We reinvestigated this 19-mer for species-specific pharmacologic profile, in vivo confirmation of resistance to inactivation by angiotensin converting enzyme (ACE), value as a module for the design of fusion proteins that bind to the B2R in mammalian species and potential activity as a histamine releaser. Competition of the binding of [3H]BK to recombinant human myc-B2Rs in cells that express these receptors revealed that MK possessed a tenuous fraction (<0.1%) of the affinity of BK, despite being only ~10-fold less potent than BK in a contractility assay based on the human isolated umbilical vein. These findings are reconciled by the generation of C-terminal fragments, like Lys-Gly-Pro-BK and Gly-Pro-BK, when the latent MK is incubated with human venous tissue (LC-MS), supporting activation via hydrolysis upstream of the BK sequence. At the rat recombinant myc-B2R, MK had a lesser affinity than that of BK, but with a narrower margin (6.2-fold, radioligand binding competition). Accordingly, MK (10 nM) stimulated calcium transients in cells that expressed the rat receptors, but not the human B2R. Recombinant MRGPRX2, a receptor that mediates cationic peptide-induced mast cell secretion, minimally responded by increased [Ca+2]i to MK at 10 μM. Enhanced green fluorescent protein fused to MK (EGFP-MK) labeled cells that expressed rat, but not human B2Rs. Intravenous MK induced dose-dependent hypotensive, vasodilator and tachycardic responses in anesthetized rats and the effects were antagonized by pretreatment with icatibant but not modified by pyrilamine or enalaprilat. Strong species-specific responses to the toxin-derived peptide MK and its prodrug status in the isolated human vein were evidenced. Accordingly, MK in the EGFP-MK fusion protein is a pharmacophore module that confers affinity for the rat B2R, but not for the human form of the B2R. MK is unlikely to be an efficient mast cell activator, but its resistance to inactivation by ACE was confirmed in vivo.
Maximakinin (MK), an amphibian peptide possessing the C-terminal sequence of bradykinin (BK), is a BK B2 receptor (B2R) agonist eliciting prolonged signaling. We reinvestigated this 19-mer for species-specific pharmacologic profile, in vivo confirmation of resistance to inactivation by angiotensin converting enzyme (ACE), value as a module for the design of fusion proteins that bind to the B2R in mammalian species and potential activity as a histamine releaser. Competition of the binding of [3H]BK to recombinant human myc-B2Rs in cells that express these receptors revealed that MK possessed a tenuous fraction (<0.1%) of the affinity of BK, despite being only ~10-fold less potent than BK in a contractility assay based on the human isolated umbilical vein. These findings are reconciled by the generation of C-terminal fragments, like Lys-Gly-Pro-BK and Gly-Pro-BK, when the latent MK is incubated with human venous tissue (LC-MS), supporting activation via hydrolysis upstream of the BK sequence. At the rat recombinant myc-B2R, MK had a lesser affinity than that of BK, but with a narrower margin (6.2-fold, radioligand binding competition). Accordingly, MK (10 nM) stimulated calcium transients in cells that expressed the rat receptors, but not the human B2R. Recombinant MRGPRX2, a receptor that mediates cationic peptide-induced mast cell secretion, minimally responded by increased [Ca+2]i to MK at 10 μM. Enhanced green fluorescent protein fused to MK (EGFP-MK) labeled cells that expressed rat, but not human B2Rs. Intravenous MK induced dose-dependent hypotensive, vasodilator and tachycardic responses in anesthetized rats and the effects were antagonized by pretreatment with icatibant but not modified by pyrilamine or enalaprilat. Strong species-specific responses to the toxin-derived peptide MK and its prodrug status in the isolated human vein were evidenced. Accordingly, MK in the EGFP-MK fusion protein is a pharmacophore module that confers affinity for the rat B2R, but not for the human form of the B2R. MK is unlikely to be an efficient mast cell activator, but its resistance to inactivation by ACE was confirmed in vivo.Three-dimensional printing for device selection in cardiology: Several key points should not be neglectedhttps://peerj.com/preprints/25972016-11-152016-11-15Hongxing LuoZhongmin Wang
We comment on the recent developments and problems of three-dimensional printing in cardiology. Since there are currently no standards or consensuses for 3D printing in clinical medicine and the technology is at its infancy in cardiology, it’s very important to detail the procedures to allow more similar studies to further our understandings of this novel technology. Most studies have employed computed tomography to obtain source data for 3D printing, the use of real-time 3D transesophageal echocardiography for data acquisition remains rare, so it would be very valuable and inspiring to detail the image postprocessing steps, or the reliability of the study results will be doubtful.
We comment on the recent developments and problems of three-dimensional printing in cardiology. Since there are currently no standards or consensuses for 3D printing in clinical medicine and the technology is at its infancy in cardiology, it’s very important to detail the procedures to allow more similar studies to further our understandings of this novel technology. Most studies have employed computed tomography to obtain source data for 3D printing, the use of real-time 3D transesophageal echocardiography for data acquisition remains rare, so it would be very valuable and inspiring to detail the image postprocessing steps, or the reliability of the study results will be doubtful.Platelets, atherothrombosis, and atherosclerosishttps://peerj.com/preprints/25862016-11-112016-11-11Karl EganFionnuala Ni AinleDermot Kenny
Cardiovascular disease is the leading cause of morbidity and mortality worldwide. In 2008 alone, 17.3 million deaths (representing 30% of all deaths) were attributable to the complications of cardiovascular disease. Of these deaths, 7.3 million were due to coronary artery disease while 6.2 million were attributable to stroke. Cardiovascular disease is expected to remain the leading cause of death globally, with the number of deaths expected to reach 23.6 million annually by 2030 (WHO statistics, 2012). Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. Arterial thrombosis on ruptured atherosclerotic plaques can lead to acute events, such as myocardial infarction (MI) and ischemic stroke. Platelets are the key cellular component of arterial thrombi with platelet adhesion under high shear conditions being central to atherothrombosis. In addition, platelets play a role in the progression of atherosclerosis. In this review, we will discuss the evidence for the role of platelets in atherothrombosis, notably the efficacy of antiplatelet agents in the prevention of ischemic events, and finally their role in the progression of atherosclerosis (atherogenesis).
Cardiovascular disease is the leading cause of morbidity and mortality worldwide. In 2008 alone, 17.3 million deaths (representing 30% of all deaths) were attributable to the complications of cardiovascular disease. Of these deaths, 7.3 million were due to coronary artery disease while 6.2 million were attributable to stroke. Cardiovascular disease is expected to remain the leading cause of death globally, with the number of deaths expected to reach 23.6 million annually by 2030 (WHO statistics, 2012). Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. Arterial thrombosis on ruptured atherosclerotic plaques can lead to acute events, such as myocardial infarction (MI) and ischemic stroke. Platelets are the key cellular component of arterial thrombi with platelet adhesion under high shear conditions being central to atherothrombosis. In addition, platelets play a role in the progression of atherosclerosis. In this review, we will discuss the evidence for the role of platelets in atherothrombosis, notably the efficacy of antiplatelet agents in the prevention of ischemic events, and finally their role in the progression of atherosclerosis (atherogenesis).Identification of suitable reference genes for real-time quantitative PCR analysis of hydrogen peroxide-treated human umbilical vein endothelial cellshttps://peerj.com/preprints/24602016-09-202016-09-20Tianyi LiHongying DiaoLei ZhaoYue XingJichang ZhangNing LiuYouyou YanXin TianWei SunBin Liu
Background. Oxidative stress could induce cell injury in vascular endothelial cells, which is the initial event in the development of atherosclerosis. Although quantitative real-time polymerase chain reaction (qRT-PCR) has been widely used in gene expression studies in oxidative stress injuries, using carefully validated reference genes has not cause sufficient attention in related researches. The objective of this study, therefore, was to select a set of stably expressed reference genes for use in qRT-PCR normalization in oxidative stress injuries in human umbilical vein endothelial cells (HUVECs) induced by hydrogen peroxide (H2O2).
Methods. HUVECs were treated with different concentrations of H2O2, geNorm and NormFinder software were conducted to evaluate the expression stabilities of 15 candidate reference genes. The optimal number of reference genes needed for qRT-PCR was determined using geNorm.
Results. Using geNorm analysis, we found that five stably expressed reference genes were sufficient for normalization in qRT-PCR analysis in HUVECs treated with H2O2. Genes with the most stable expression according to geNorm were U6 and TFRC, RPLP0, GAPDH and ACTB, and were ALAS1, TFRC, U6, GAPDH, and ACTB according to NormFinder.
Discussion. Taken together, our study demonstrated that the expression stability of reference genes may differ according to the statistical program used. U6, TFRC, RPLP0, GAPDH, and ACTB was the optimal set of reference genes for studies on gene expression with qRT-PCR assays in HUVECs under oxidative stress study.
Background. Oxidative stress could induce cell injury in vascular endothelial cells, which is the initial event in the development of atherosclerosis. Although quantitative real-time polymerase chain reaction (qRT-PCR) has been widely used in gene expression studies in oxidative stress injuries, using carefully validated reference genes has not cause sufficient attention in related researches. The objective of this study, therefore, was to select a set of stably expressed reference genes for use in qRT-PCR normalization in oxidative stress injuries in human umbilical vein endothelial cells (HUVECs) induced by hydrogen peroxide (H2O2).Methods. HUVECs were treated with different concentrations of H2O2, geNorm and NormFinder software were conducted to evaluate the expression stabilities of 15 candidate reference genes. The optimal number of reference genes needed for qRT-PCR was determined using geNorm.Results. Using geNorm analysis, we found that five stably expressed reference genes were sufficient for normalization in qRT-PCR analysis in HUVECs treated with H2O2. Genes with the most stable expression according to geNorm were U6 and TFRC, RPLP0, GAPDH and ACTB, and were ALAS1, TFRC, U6, GAPDH, and ACTB according to NormFinder.Discussion. Taken together, our study demonstrated that the expression stability of reference genes may differ according to the statistical program used. U6, TFRC, RPLP0, GAPDH, and ACTB was the optimal set of reference genes for studies on gene expression with qRT-PCR assays in HUVECs under oxidative stress study.