Journal of Cardiovascular Pharmacology and Therapeutics最新文献

{"title":"Understanding the Mechanism of Drug Transfer and Retention of Drug-Coated Balloons.","authors":"Estefanny Villar-Matamoros,&nbsp;Lauren Stokes,&nbsp;Alyssa Lloret,&nbsp;Meagan Todd,&nbsp;Bryan W Tillman,&nbsp;Saami K Yazdani","doi":"10.1177/10742484221119559","DOIUrl":"https://doi.org/10.1177/10742484221119559","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study was to determine the impact of varying inflation parameters on paclitaxel delivery and retention using a commercially available DCB.</p><p><strong>Background: </strong>Drug-coated balloons (DCB) have become the standard treatment for peripheral artery disease. Clinical data suggest that varying DCB delivery parameters directly impact patient outcome. Differences in delivery parameters can potentially alter the retention of the drug coating on DCBs.</p><p><strong>Methods: </strong>Harvested porcine carotid arteries were utilized in an <i>ex vivo</i> pulsatile flow bioreactor system. The DCBs were then deployed at a DCB-to-artery ratio of 1:1 or 1.25:1, an inflation time of 30 seconds or 1 minute and transit time of 30 seconds or 3 minutes. The amount of drug retention in arterial tissue was evaluated by pharmacokinetic analysis at 1 hour and 1 day post DCB deployment.</p><p><strong>Results: </strong>Arterial paclitaxel levels were found to be less at an inflation ratio of 1:1 with 3-minute transit time as compared to 30 seconds of transit time at 1 hour (12.3 ± 1.6 ng/mg vs. 391 ± 139 ng/mg, <i>P</i> = .036). At 1-day, DCBs deployed at a ratio of 1:1 resulted in less drug retention as compared to 1.25:1 (61.3 ± 23.1 ng/mg vs. 404 ± 195 ng/mg, <i>P</i> = .013).</p><p><strong>Conclusion: </strong>Arterial paclitaxel retention is reduced with extended transit times and sub-optimal expansion of the balloon. Optimization of delivery parameters can serve as an effective strategy to enhance clinical DCB outcomes.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":"10742484221119559"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/32/nihms-1839308.PMC9549471.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40712824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Homoarginine on Myocardial Function and Remodeling in a Rat Model of Chronic Renal Failure.","authors":"Vitali Koch,&nbsp;Christophe Weber,&nbsp;Johannes H Riffel,&nbsp;Kristina Buchner,&nbsp;Sebastian J Buss,&nbsp;Selina Hein,&nbsp;Derliz Mereles,&nbsp;Marco Hagenmueller,&nbsp;Christian Erbel,&nbsp;Winfried März,&nbsp;Christian Booz,&nbsp;Moritz H Albrecht,&nbsp;Thomas J Vogl,&nbsp;Norbert Frey,&nbsp;Stefan E Hardt,&nbsp;Marco Ochs","doi":"10.1177/10742484211054620","DOIUrl":"https://doi.org/10.1177/10742484211054620","url":null,"abstract":"<p><strong>Purpose: </strong>Low plasma concentrations of the amino acid homoarginine (HA) have been shown to correlate with adverse cardiovascular outcome, particularly in patients with chronic kidney disease. The present study sought to investigate the effect of HA treatment on cardiac remodeling in rats undergoing artificially induced renal insufficiency by 5/6 nephrectomy (5/6 Nx).</p><p><strong>Methods: </strong>A total of 33 male Wistar rats were randomly divided into sham and 5/6 Nx groups, receiving either placebo treatment or 400 mg·kg^-1·day^-1 HA over a 4-week period.</p><p><strong>Results: </strong>5/6 Nx per se resulted in adverse myocardial remodeling with aggravated cardiac function and associated cardiac overload as the most obvious alteration (-23% ejection fraction, <i>P</i> < 0.0001), as well as increased myocardial fibrosis (+80%, <i>P</i> = 0.0005) compared to placebo treated sham animals. HA treatment of 5/6 Nx rats has led to an improvement of ejection fraction (+24%, <i>P</i> = 0.0003) and fractional shortening (+21%, <i>P</i> = 0.0126), as well as a decrease of collagen deposition (-32%, <i>P</i> = 0.0041), left ventricular weight (-14%, <i>P</i> = 0.0468), and myocyte cross-sectional area (-12%, <i>P</i> < 0.0001). These changes were accompanied by a downregulation of atrial natriuretic factor (-65% <i>P</i> < 0.0001) and collagen type V alpha 1 chain (-44%, <i>P</i> = 0.0006). Sham animals revealed no significant changes in cardiac function, myocardial fibrosis, or any of the aforementioned molecular changes after drug treatment.</p><p><strong>Conclusion: </strong>Dietary HA supplementation appears to have the potential of preventing cardiac remodeling and improving heart function in the setting of chronic kidney disease. Our findings shed new light on HA as a possible new therapeutic agent for patients at high cardiovascular risk.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":"10742484211054620"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39794841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Detection of Atrial Fibrillation in Community Pharmacies-CRIFAFARMA Study.","authors":"María González Valdivieso,&nbsp;Domingo Orozco-Beltrán,&nbsp;Adriana López-Pineda,&nbsp;Vicente Francisco Gil-Guillén,&nbsp;José A Quesada,&nbsp;Concepción Carratalá-Munuera,&nbsp;Rauf Nouni-García","doi":"10.1177/10742484221078973","DOIUrl":"https://doi.org/10.1177/10742484221078973","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) is the most common arrhythmia to appear in clinical practice. People with AF have 5 times the risk of stroke compared to the general population.</p><p><strong>Objective: </strong>This study aimed to determine the prevalence of AF in people over the age of 50 without known AF, who presented to a community pharmacy to check their cardiovascular risk factors, to identify risk factors associated with AF, and to assess the risk of stroke in people who screened positive for AF.</p><p><strong>Methods: </strong>A multicenter observational descriptive study of a screening program took place from May to December 2016. A blood pressure monitor (Microlife Watch BP Home) was used to screen for AF, and the CHA2DS2-VASc questionnaire was used to assess stroke risk.</p><p><strong>Results: </strong>The study included 452 adults over the age of 50. The CRIFAFARMA study detected a prevalence of AF of 9.1%. Risk factors for AF were: age of 75 years or older (<i>P</i> = .024), lack of physical activity (<i>P</i> = .043), diabetes (<i>P</i> < .001), dyslipidemia (<i>P</i> = .003), and history of cardiovascular disease (<i>P</i> = .003). Diabetes (OR 2.79, <i>P</i> = .005) and dyslipidemia (OR 2.16, <i>P</i> = .031) had a combined explanatory capacity in the multivariable logistic regression model adjusted for age. 85% were at high risk of stroke according to the CHA2DS2-VASc scale.</p><p><strong>Conclusions: </strong>AF was detected in more than 9% of the included population. Factors associated with AF were advanced age, lack of physical activity, diabetes, dyslipidemia, and history of cardiovascular disease, with diabetes and dyslipidemia standing out as the factors with independent explanatory capacity.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":"10742484221078973"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39824806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Valproic Acid Use With Post-Myocardial Infarction Heart Failure Development: A Meta-Analysis of Two Retrospective Case-Control Studies.","authors":"Joseph D English, Shuo Tian, Zhong Wang, Jasmine A Luzum","doi":"10.1177/10742484221140303","DOIUrl":"10.1177/10742484221140303","url":null,"abstract":"<p><strong>Background: </strong>Despite advances in treatments, myocardial infarction (MI) remains a significant cause of morbidity and mortality worldwide. Our team has previously shown that valproic acid (VPA) is cardio-protective when administered to rats post-MI. The aim of this study was to investigate the association of VPA use with post-MI heart failure (HF) development in humans.</p><p><strong>Methods: </strong>This study was a random effects meta-analysis of two retrospective case-control studies collected from electronic health record (Michigan Medicine) and claims data (OptumInsight). Cases with an active prescription for VPA at the time of their MI were matched 1:4 to controls not taking VPA at the time of their MI by multiple demographic and clinical characteristics. The primary outcome, time-to-HF development, was analyzed using the Fine-Gray competing risks model of any VPA prescription versus no VPA prescription. An exploratory analysis was conducted to evaluate the association of different VPA doses (≥1000 mg/day vs <1000 mg/day vs 0 mg/day VPA).</p><p><strong>Results: </strong>In total, the datasets included 1313 patients (249 cases and 1064 controls). In the meta-analysis, any dose of VPA during an MI tended to be protective against incident HF post-MI (HR = 0.87; 95% CI = 0.72-1.01). However, when stratified by dose, high-dose VPA (≥1000 mg/day) significantly associated with 30% reduction in risk for HF post-MI (HR = 0.70; 95% CI = 0.49-0.91), whereas low-dose VPA (<1000 mg/day) did not (HR = 0.95; 95% CI = 0.78-1.13).</p><p><strong>Conclusion: </strong>VPA doses ≥1000 mg/day may provide post-MI cardio-protection resulting in a reduced incidence of HF.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221140303"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/98/nihms-1861271.PMC9841513.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiplatelet Therapy and Bleeding Outcomes With CYP2C19 Genotyping.","authors":"James C Coons,&nbsp;James M Stevenson,&nbsp;Ami Patel,&nbsp;A J Conrad Smith,&nbsp;Linda Prebehalla,&nbsp;Philip E Empey","doi":"10.1177/10742484221143246","DOIUrl":"https://doi.org/10.1177/10742484221143246","url":null,"abstract":"<p><strong>Purpose: </strong>The impact of antiplatelet therapy with availability of CYP2C19 genotyping on bleeding in a real-world setting has not been extensively studied.</p><p><strong>Methods: </strong>Prospective, single-center, cohort study conducted between December 2015 and October 2019 with 1-year follow-up. Patients underwent percutaneous coronary intervention (PCI), CYP2C19 genotyping, and received P2Y12 inhibitor therapy. The primary outcome was time to first bleed of any severity using Bleeding Academic Research Consortium criteria. Secondary outcomes included time to first major bleed and rates of antiplatelet switching.</p><p><strong>Results: </strong>The primary outcome occurred in 697 of 2091 (33%) participants at a median of 15 days. Major bleeding occurred in 176 (8%) of patients. Compared to clopidogrel, treatment with ticagrelor or prasugrel was associated with increased risk of any bleeding (adjusted HR [aHR] 2.04, 95% CI 1.69-2.46). For patients without CYP2C19 no function alleles, treatment with prasugrel or ticagrelor was associated with increased risk of any bleeding (aHR 2.31, 95% CI 1.83-2.90). Similar associations were observed for major bleeding. No difference in ischemic events was observed. Among patients discharged on ticagrelor or prasugrel, 199 (36%) were de-escalated to clopidogrel within 1 year. De-escalation was more likely after a bleed if patients did not have a no function allele (35.9% vs 19.1%; <i>P</i> = .02).</p><p><strong>Conclusion: </strong>Bleeding is common in post-PCI patients on antiplatelet therapy. Patients on high potency agents had higher bleeding risk in the population at-large and in non-carriers of CYP2C19 no function alleles. Genotype-guided antiplatelet de-escalation should be further explored in prospective studies.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221143246"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10354586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 3 Randomized Controlled Trial to Evaluate Efficacy and Safety of New-Formulation Zenon (Rosuvastatin/Ezetimibe Fixed-Dose Combination) in Primary Hypercholesterolemia Inadequately Controlled by Statins.","authors":"Alberico L Catapano,&nbsp;Michal Vrablik,&nbsp;Yuri Karpov,&nbsp;Baptiste Berthou,&nbsp;Megan Loy,&nbsp;Marie Baccara-Dinet","doi":"10.1177/10742484221138284","DOIUrl":"https://doi.org/10.1177/10742484221138284","url":null,"abstract":"<p><strong>Objective: </strong>In primary hypercholesterolemia many people treated with statins do not reach their plasma LDL-C goals and are at increased risk of cardiovascular disease (CVD). This study aimed to evaluate efficacy and safety of a new fixed-dose combination (FDC) formulation of rosuvastatin/ezetimibe (R/E) in this population.</p><p><strong>Methods: </strong>This was a multicenter, multinational, randomized, double-blind, double-dummy, active-controlled, parallel-arm study of FDC R/E in people with primary hypercholesterolemia at very high risk (VHR) or high risk (HR) of CVD, inadequately controlled with 20 mg or 10 mg stable daily dose of rosuvastatin or equipotent dose of another statin. The primary objective was to demonstrate superiority of FDC R/E versus rosuvastatin monotherapy uptitrated to 40 mg (R40) or 20 mg (R20) in reduction of LDL-C after 6 weeks.</p><p><strong>Results: </strong>Randomized VHR participants (n = 244) were treated with R40, R40/E10, or R20/E10; randomized HR participants (n = 208) received R10/E10 or R20. In VHR participants, superiority of R40/E10 and R20/E10 versus R40 was demonstrated on LDL-C percent change from baseline to Week 6 with least squares mean differences (LSMD) of -19.66% (95% CI: -29.48% to -9.84%; <i>P</i> < .001) and -12.28% (95% CI: -22.12% to -2.44%; <i>P</i> = .015), respectively. In HR participants, superiority of R10/E10 over R20 was not demonstrated (LSMD -5.20%; 95% CI: -15.18% to 4.78%; <i>P</i> = .306), despite clinically relevant LDL-C reduction with R10/E10. No unexpected safety findings were reported.</p><p><strong>Conclusions: </strong>The results from this study suggest that R/E FDCs improve LDL-C reduction and goal achievement in people with primary hypercholesterolemia inadequately controlled with statins and at VHR/HR of CVD.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221138284"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10466359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis.","authors":"Jorge L Reyes,&nbsp;Charles A Herzog,&nbsp;Heng Yan,&nbsp;Nicholas S Roetker,&nbsp;James B Wetmore","doi":"10.1177/10742484221142220","DOIUrl":"https://doi.org/10.1177/10742484221142220","url":null,"abstract":"<p><strong>Background: </strong>The association of patient and prescriber characteristics with use of warfarin versus direct-acting oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is not well studied.</p><p><strong>Methods: </strong>The 20% Centers for Medicare & Medicaid Services Parts A, B, and D claims data from 2010 to 2017 were used to identify patients with stage 3, 4, or 5 CKD and AF who received a DOAC (apixaban, dabigatran, rivaroxaban) or warfarin. Prescribers were categorized as cardiologists, primary care providers (PCPs), and others. Using logistic regression, we estimated odds ratios (ORs) for the association of baseline characteristics and prescriber specialty with first use of a DOAC, relative to warfarin.</p><p><strong>Results: </strong>We identified 22,739 individuals with CKD who were newly initiated on oral anticoagulation for AF. New DOAC prescriptions increased from 490 in 2011 to 3261 in 2017, and displaced warfarin over time (1849, 2011; 945, 2017). By Q4 of 2014, cardiologists prescribed DOACs as initial treatment more frequently than warfarin, but non-cardiologists did not do so until 2015. As of 2017, apixaban was the most widely prescribed anticoagulant, comprising 56% and 50% of prescriptions by cardiologists and non-cardiologists, respectively. PCPs (OR 0.54, 0.51-0.58) and other providers (OR 0.55, 0.51-0.59) were less likely than cardiologists to prescribe DOACs.</p><p><strong>Conclusions: </strong>DOAC prescriptions, particularly apixaban, increased over time and gradually displaced warfarin. The total number of patients with AF and CKD receiving anticoagulation increased over time. Cardiologists increased DOAC prescriptions more rapidly than non-cardiologists.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221142220"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10479707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection.","authors":"Wasim S El Nekidy,&nbsp;Khalid Almuti,&nbsp;Hazem ElRefaei,&nbsp;Bassam Atallah,&nbsp;Lana M Mohammad,&nbsp;Wael AlMahmeed,&nbsp;Mohamed Badr,&nbsp;Khaled Abdallah,&nbsp;Fadi Hamed,&nbsp;Jihad Mallat","doi":"10.1177/10742484211069479","DOIUrl":"https://doi.org/10.1177/10742484211069479","url":null,"abstract":"<p><strong>Background: </strong>Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms).</p><p><strong>Results: </strong>Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], <i>P</i> < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], <i>P</i> = .04), and male gender (95% vs. 82.8%, <i>P</i> = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (<i>P</i> = .004 for the likelihood-ratio test).</p><p><strong>Conclusion: </strong>The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":"10742484211069479"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39803409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling.","authors":"Sergey V Popov,&nbsp;Ekaterina S Prokudina,&nbsp;Alexander V Mukhomedzyanov,&nbsp;Natalia V Naryzhnaya,&nbsp;Huijie Ma,&nbsp;Jitka M Zurmanova,&nbsp;Peter F M van der Ven,&nbsp;Leonid N Maslov","doi":"10.1177/1074248420985301","DOIUrl":"https://doi.org/10.1177/1074248420985301","url":null,"abstract":"<p><p>Despite the recent progress in research and therapy, cardiovascular diseases are still the most common cause of death worldwide, thus new approaches are still needed. The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKCε) and extracellular signal-regulated kinase (ERK1/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"575-584"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1074248420985301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39286851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?","authors":"Ruihai Zhou,&nbsp;George A Stouffer,&nbsp;Sidney C Smith","doi":"10.1177/10742484211023632","DOIUrl":"https://doi.org/10.1177/10742484211023632","url":null,"abstract":"<p><p>Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as \"bad\" cholesterol and high-density lipoprotein cholesterol (HDL-C) as \"good\" cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"533-549"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/10742484211023632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39246501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}