Bringing Journal of Cardiovascular Pharmacology and Therapeutics (JCPT) to a Next Level: Strategies and Vision to Ensure a Sustained Journal Growth.

Increased production of reactive oxygen species (ROS) in the vascular wall is a characteristic feature of disease states, including atherosclerosis, diabetes and hypertension. ROS, such as superoxide, reduce nitric oxide bioactivity by scavenging and cause oxidation of lipids and target proteins. In addition, recent work has revealed that ROS mediate a wide range of pathological processes in the endothelium, smooth muscle cells, and inflammatory cells.1 ROS are generated by enzyme systems present in cells in the vascular wall, including NAD(P)H oxidase, xanthine oxidase, and nitric oxide synthase. The activities and levels of these enzyme systems are increased in association with vascular disease risk factors2 and in vascular disease states in which oxidative stress is prominent, for example, in diabetes3 and atherosclerosis. See page 1838 The NAD(P)H oxidases appear to be particularly important sources of ROS production in blood vessels,4 where they are constitutively active, producing relatively low levels of ROS under basal conditions, but generating higher levels of oxidants in response to stimuli such as growth factors and cytokines. These factors are consistent with a role for nonphagocytic NAD(P)H oxidases in cellular signaling rather than the high-level burst activity characteristic of the phagocyte NAD(P)H oxidase. The NAD(P)H oxidases are multimeric enzymes composed of plasma membrane associated–proteins as well as cytosolic factors. In the phagocytic-type NAD(P)H oxidase, the plasma membrane–associated proteins gp91phox and p22phox compose the flavocytochrome b558 complex, which forms the catalytic subunit of the oxidase. The cytosolic subunits, including p47phox, p67phox, and the G-protein Rac, provide regulatory function. Azumi and colleagues,5 in this issue of Arteriosclerosis, Thrombosis and Vascular Biology …

This reference summarizes recent advancements in knowledge about cardiovascular disease and pharmacology. The goal of the book is to inform readers about recent findings on cardiovascular therapeutics and how to conduct experiments to evaluate natural products. It presents 10 chapters that cover basic clinical research on cardiovascular diseases and therapeutic agents derived from natural sources. The book concludes with a series of experiments that demonstrate the methods to test the ameliorative effects of 3 phytochemicals: Biochanin A (red clover), Zingiberene (ginger oil) and Betaine (sugar beet). Key Features - 10 chapters that highlight recent research cardiovascular medicine and pharmacology - Covers knowledge about basic cardiovascular physiology, congestive heart failure treatment and the treatment of heart inflammation. - Covers uses, benefits, and drawbacks of numerous rodent and non-rodent animal models for studying CVD - Updates readers about 21st-century CRISPR-cas9 technology and its uses in CVD. - Covers the significance of Indian Ayurvedic techniques on the cardiovascular system, - Covers information about nutraceuticals for CVD therapy - Includes experiments to evaluate 3 phytochemicals for the treatment of different heart diseases such as hypertension, obesity-cardiomyopathy and the mitigation of inflammatory cytokines in myocardial infarction. This book is an informative resource for cardiologists, and researchers working in the field of cardiovascular pharmacology. It also helps readers to understand the benefits of herbal medications that are commonly available for consumption in homes.

During the past decade, numerous experimental and clinical studies have demonstrated that many common conditions predisposing to atherosclerosis, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with a reduced vascular availability of nitric oxide (NO•). Nitric oxide not only produces vasodilation but also has potent antiatherogenic properties. These properties include inhibition of platelet aggregation, prevention of smooth muscle cell proliferation, reduction of lipid peroxidation, and inhibition of adhesion molecule expression. Thus, the loss of NO• observed in these various conditions not only alters vascular tone but also may explain in part why these conditions are risk factors for atherosclerosis. See p 2673 Given this apparent link between loss of nitric oxide and atherosclerosis, several groups have been interested in the concept that endothelium-dependent vasodilation, a surrogate for NO• bioavailability, may predict cardiovascular events. Indeed, Suwaidi et al1 followed 157 patients with mildly diseased coronary arteries for an average of 28 months and observed cardiac events only in the patients with the lowest tertile of coronary vasodilation to acetylcholine. Similarly, in a study of 147 patients, Schachinger et al2 used 3 different stimuli for endothelial release of NO: acetylcholine, cold pressor testing, and increased blood flow. The authors showed that responses to each of these stimuli were independent predictors of cardiovascular events during a follow-up period of ≈8 years. Perticone et al3 also demonstrated that endothelial dysfunction in the forearm circulation predicts cardiovascular events in hypertensive subjects. There have been several explanations for why the various risk factors impair endothelial function. One that has received substantial attention is increased production of reactive oxygen species within the vessel.4 In particular, superoxide (O2•-) reacts rapidly with NO•, resulting in the formation of the peroxynitrite anion and loss of NO• …

Elevated low-density lipoprotein cholesterol (LDLC) levels in the plasma is the most important causative factor of atherosclerosis and associated ischemic cardiovascular diseases. The LDL receptor (LDLR) is the preferential pathway through which LDLs are cleared from the circulation. LDLs bound to the LDLR are internalized into clathrin-coated pits and subsequently undergo lysosomal degradation, whereas the LDLR is recycled back to the plasma membrane. See accompanying article on page 1333 Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with elevated LDL levels and premature coronary heart disease. FH is caused primarily by mutations of the LDLR or of apolipoprotein B100 (apoB100), the protein component of LDL that interacts with the LDLR. In 2003, “gain of function” mutations on a newly identified gene, proprotein convertase subtilisin/kexin type 9 ( PCSK9), were associated with FH. In 2005, a causative association was established between “loss of function” mutations in PCSK9 and low LDLC levels in 2% of the African-American population. The coronary heart disease risk in these individuals was reduced by 88%. As a result of these landmark studies (reviewed in Reference 1), PCSK9 became the subject of intensive research to discover the underlying mechanisms. PCSK9 is a serine protease mainly expressed in the liver and the intestine. It acts by reducing the amount of LDLR in hepatocytes. This was demonstrated in vitro and in mouse models …

British Journal of Hospital MedicineVol. 81, No. 7 Case ReportMultiple spontaneous coronary thrombosis causing ST-elevation myocardial infarction in a patient with COVID-19Hibba Kurdi, Daniel R Obaid, Zia UlHaq, Adrian Ionescu, Baskar SekarHibba KurdiCorrespondence to: Hibba Kurdi; E-mail Address: [email protected]Morriston Cardiology Centre, Morriston Hospital, Swansea, UKSearch for more papers by this author, Daniel R ObaidMorriston Cardiology Centre, Morriston Hospital, Swansea, UKSearch for more papers by this author, Zia UlHaqMorriston Cardiology Centre, Morriston Hospital, Swansea, UKSearch for more papers by this author, Adrian IonescuMorriston Cardiology Centre, Morriston Hospital, Swansea, UKSearch for more papers by this author, Baskar SekarMorriston Cardiology Centre, Morriston Hospital, Swansea, UKSearch for more papers by this authorHibba Kurdi; Daniel R Obaid; Zia UlHaq; Adrian Ionescu; Baskar SekarPublished Online:13 Jul 2020https://doi.org/10.12968/hmed.2020.0337AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Bangalore S, Sharma A, Slotwiner A et al.. ST-segment elevation in patients with Covid-19: a case series. N Engl J Med. 2020;382(25):2478–2480. https://doi.org/10.1056/NEJMc2009020 Crossref, Medline, Google ScholarBikdeli B, Madhavan MV, Jimenez D et al.. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020;75(23):2950–2973. https://doi.org/10.1016/j.jacc.2020.04.031 Crossref, Medline, Google ScholarBritish Society of Thoracic Imaging. Radiology decision tool for suspected COVID-19. 2020. https://www.bsti.org.uk/media/resources/files/NHSE_BSTI_APPROVED_Radiology_on_CoVid19_v6_ucQ1tNv.pdf (accessed 24 June 2020) Google ScholarChoi S, Jang WJ, Song YB et al.. D-dimer levels predict myocardial injury in ST-segment elevation myocardial infarction: a cardiac magnetic resonance imaging study. PLoS One. 2016;11(8):e0160955–e0160955. https://doi.org/10.1371/journal.pone.0160955 Crossref, Medline, Google ScholarCorrales-Medina VF, Alvarez KN, Weissfeld LA et al.. Association between hospitalization for pneumonia and subsequent risk of cardiovascular disease. JAMA. 2015;313(3):264–274. https://doi.org/10.1001/jama.2014.18229 Crossref, Medline, Google ScholarFang Y, Zhang H, Xie J et al.. Sensitivity of chest CT for COVID-19: comparison to RT-PCR. Radiology. 2020;19:200432. https://doi.org/10.1016/j.crad.2020.03.008 Crossref, Google ScholarThachil J. The versatile heparin in COVID-19. J Thromb Haemost. 2020;18(5):1020–1847. https://doi.org/10.1111/jth.14821 Crossref, Medline, Google ScholarWatson J, Whiting PF, Brush JE. Interpreting a COVID-19 test result. BMJ. 2020;369:m1808. https://doi.org/10.1136/bmj.m1808 Medline, Google ScholarXiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020;41(19):1798–1800. https://doi.org/10.1093/eurheartj/ Crossref, Medline, Google Scholar FiguresReferencesRelatedDetailsCited byRole of Acute Thrombosis in Coronavirus Disease 2019Critical Care Clinics, Vol. 38, No. 3The day after tomorrow: cardiac surgery and coronavirus disease-20198 December 2021 | Journal of Cardiovascular Medicine, Vol. 23, No. 2Coronary Stent Thrombosis in COVID-19 Patients: A Systematic Review of Cases Reported Worldwide27 January 2022 | Viruses, Vol. 14, No. 2Selective intracoronary administration of glycoprotein IIb/IIIa inhibitors for acute myocardial infarction in a patient with COVID-19 during percutaneous coronary interventionKardiologiya i serdechno-sosudistaya khirurgiya, Vol. 15, No. 2COVID-19 and Acute Myocardial Injury and Infarction: Related Mechanisms and Emerging Challenges5 May 2021 | Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 26, No. 5A Review of Coronary Artery Thrombosis: A New Challenging Finding in COVID-19 Patients and ST-elevation Myocardial InfarctionCurrent Problems in Cardiology, Vol. 46, No. 3COVID-19 Infection: Viral Macro- and Micro-Vascular Coagulopathy and Thromboembolism/Prophylactic and Therapeutic Management14 September 2020 | Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 26, No. 1Hematologic Emergencies in Patients with Covid-1918 November 2021Therapeutic Implications of COVID-19 for the Interventional Cardiologist17 December 2020 | Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 378 2 July 2020Volume 81Issue 7ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 13 July 2020 Published in print 2 July 2020 Information© MA Healthcare LimitedPDF download

There are considerable data to support the general hypothesis that accumulation of [Na+]i during ischemia and early reperfusion leads, via Na+/Ca2+ exchange, to elevated [Ca2+]i, resulting in myocardial damage.1 2 3 4 5 6 7 8 9 10 Despite the strong support for the general aspects of this hypothesis, there is controversy regarding some details that have important implications for the design of therapeutic interventions. The relative importance of the increase in [Na+]i during ischemia versus the increase in [Na+]i during reperfusion in contributing to the rise in [Ca2+]i and resultant injury is debated. These issues are important because it has been suggested that inhibition of the Na+/H+ exchanger (NHE) during reperfusion alone would be beneficial. This would allow clinical intervention after an ischemic episode. It is also important to understand why an increase in [Na+]i is detrimental. It is commonly assumed that [Na+]i is detrimental because it leads to increased [Ca2+]i during reperfusion, either due to diminished Ca2+ efflux via Na+/Ca2+ exchange or due to increased Ca2+ influx due to reverse Na+/Ca2+ exchange. Recent data presented by Cross et al9 suggest that reverse Na+/Ca2+ exchange is involved in postischemic contractile dysfunction. However, an increase in [Na+]i could also be detrimental because of effects on K+ loss11 or energetics. An understanding of the mechanism responsible for the detrimental effects of Na+ accumulation is important for the design of therapeutic interventions. A study12 published in this issue of Circulation Research adds new insight into these important issues. Lazdunski et al …

featured in this issue of Circulation presents data showingthat pyruvate, which dose-dependently improved perfor-mance in myocardium from failing human hearts, may be onesuch agent.A number of abnormalities in both energy metabolism andcontractile function have been identified in failing cardiacmuscle. Metabolic changes include decreases in high energyphosphorylation potential, decreases in mitochondrial oxida-tive phosphorylation capacity, and a switch to a more fetalglycolytic metabolism.

Book reviews in this article: Cardiovascular Pharmacology and Therapeutics. Edited by Bramah N. Singh, Victor J. Dzau, Paul M. Vanhoutte, and Raymond L. Woosley. Vascular Diseases: Surgical and Interventional Therapy. Edited by D. Eugene Strandness, Jr., and Arina van Breda.

Why a New Journal in Cardiovascular Pharmacology and Therapeutics?

The traditional paradigm for heart failure management centered on mitigating the hemodynamic changes that occur in response to the failing heart. Subsequently, pharmacological modulation of neurohormonal activation and more recently cardiac resynchronization have been shown to reverse ventricular remodeling and to slow disease progression. Despite these advances in therapy, successful treatment of heart failure remains challenging, with rates of hospitalization in the United States exceeding 1 million per year and the annual number of heart failure–related deaths increasing steadily.1 Unfortunately, the history of drug development for heart failure has been marked by many disappointments, most notably the excess mortality associated with oral positive inotropes that were targeted at improving hemodynamics. In addition, more recent interventions aimed at interrupting endothelin and cytokine signaling or reducing oxidative stress have yet to fulfill hopes for novel biological therapies. Thus, new therapeutic strategies are needed to alter the natural history of the disease and to slow or reverse current epidemiological trends. The report by Lee and colleagues2 in this issue of Circulation points toward the promise of an alternative approach based on favorably influencing the efficiency of myocardial energetics, thereby increasing cardiac performance without depending on changes in oxygen consumption or improvement in hemodynamics. Article p 3280 The study of agents aimed at enhancing myocardial energy efficiency has focused principally on shifting myocardial substrate use toward more oxygen-efficient pathways.3 Although the complete oxidation of fatty acids to CO2 yields more adenosine triphosphate (ATP) per molecule of CO2 produced than does complete oxidation of glucose, a greater amount of oxygen is required to completely oxidize a fatty acid of equivalent carbon-chain length. Therefore, for a given amount of oxygen consumed, metabolism of glucose is more “oxygen efficient,” producing ≈15% more ATP (Figure).3,4 Production of ATP and consumption of …

The heart makes its living by liberating energy from a variety of oxidizable substrates, either simultaneously or vicariously.1 Because of built-in mechanisms that choose the most efficient substrate for a given physiological environment, the heart is a true metabolic omnivore.2 The link between metabolism and function of the heart was discovered by Langendorff3 when he demonstrated that the mammalian heart receives oxygen and nutrients through the coronary circulation and not through the endocardium, as it had been assumed until then. Early investigators also knew already that the heart oxidizes fatty acids and glucose,4 and myocardial fuel economy became a focus of biochemical investigation in the 1960s. Biochemists “discovered” the heart as a convenient bag of enzymes to study muscle metabolism and found that fatty acids suppress glucose oxidation, chiefly at the level of the pyruvate dehydrogenase complex.5 Conversely, we later found that glucose suppresses fatty acid oxidation,1 chiefly at the level of fatty acid entry into the mitochondria. In short, fuel metabolism in the heart is highly regulated, allowing the heart to respond to substrate availability, circulating hormones (such as insulin or catecholamines), coronary flow, and workload by choosing the “right” substrate at the right moment. Unless blood supply is curtailed, as it is the case in ischemia, the heart is never short of fuel to burn. See p 2125 What is, then, the principle that underlies substrate switching? As every nutritionist knows, fat has a higher caloric value than carbohydrates; at the same time, the oxidation of carbohydrates results in more efficient energy production than the oxidation of fat. The heart readily oxidizes both substances. Substrate switching in the heart is determined by an interaction of control and regulation of the metabolism of energy providing substrates. According to the metabolic control theory,6 …

Diabetes mellitus is a major risk factor for the development of atherosclerosis.1 Although there has been a significant amount of work examining histological factors which predispose to plaque rupture and subsequent acute coronary syndromes,2 less is known about the role of plaque and vessel biomechanical properties. We have previously shown using intravascular ultrasound (IVUS), that there is a significant change in coronary plaque area between systole and diastole, and this is a major determinant of coronary compliance.3 In the current study we used IVUS to assess coronary plaque characteristics in individuals with and without type 2 diabetes mellitus. All patients scheduled for percutaneous coronary intervention of lesions in the circumflex or left anterior descending (LAD) arteries were considered eligible for inclusion, other than those undergoing emergent revascularization for acute myocardial infarction. Diabetic patients were identified as those who had their diabetes diagnosed in adult life with biochemical confirmation including a fasting glucose >7.0 mmol/L. The study was approved by the Human Ethics Committee of the Alfred Hospital. Collection …

While sympathetic stimulation of the heart produces chronotropic, inotropic, and lusitropic effects, increased frequency alone causes a positive force-frequency relationship (FFR) and frequency-dependent acceleration of relaxation (FDAR).1 That is, contraction amplitude and relaxation rate are increased with increasing frequency in most species (including humans). The key mechanism involved in the positive FFR is increased sarcoplasmic reticulum (SR) Ca2+ load, due to increased Ca2+ influx and decreased Ca2+ efflux.1,2 Ca2+ influx increases due to more L-type Ca2+ current ( I Ca) per unit time, while Ca2+ efflux via Na+-Ca2+ exchange (NCX) decreases because the diastolic time is reduced and [Na+]i increases. Enhanced SR Ca2+-pump function causes FDAR and also augments SR Ca2+ loading. Various signaling pathways are involved (eg, CaMKII).3 In human heart failure, the FFR reverses (ie, from positive to negative) due to an inability of the SR to increase Ca2+ content.4 This negative FFR is a main contributor to the loss of contractile reserve in the failing heart. Of many pathways that can modify FFR, nitric oxide (NO) signaling is the topic addressed by Khan et al in this issue of Circulation Research .5 NO synthase (NOS) produces NO from l-arginine, and cardiac myocytes express all three NOS isoforms.6,7 NOS1 (nNOS) and NOS3 (eNOS) are constitutively expressed and produce low amounts of NO (regulated by [Ca2+-calmodulin]i levels). NOS2 (iNOS) …

Congestive heart failure is a leading cause of cardiovascular mortality in the United States and Europe.1 Clinically, this syndrome is characterized by water retention and often left ventricular dilatation with poor systolic contractility. Etiologically, congestive heart failure can be of genetic or acquired origin. In 1993, 2 groups independently reported mutations in the cytoskeletal protein dystrophin as the cause of X-linked dilated cardiomyopathy, a rare inheritable disease that leads to enlargement of ventricular dimensions and to congestive heart failure.1 Over the last decade, the pathophysiological relevance of the cardiac myocyte cytoskeleton for the development of congestive heart failure is being increasingly recognized. See p 1424 For a coordinated contractile function of the heart, the mechanical forces generated within the sarcomeres of individual cardiac myocytes are transmitted to the extracellular matrix.2 For this purpose, cardiac myocytes are equipped with a specialized extrasarcomeric cytoskeleton. The cardiac myocyte cytoskeleton acts as a “scaffold” that provides mechanical stability to transmit the periodic shortening of the sarcomeres to adjacent cardiac myocytes.1 Additionally, the cytoskeleton possesses important signaling properties.3 The critical importance of an intact cytoskeleton for normal cardiac function in humans and rodents is highlighted by genetic defects in the cytoskeletal proteins titin, actin, dystrophin, sarcoglycans, and others, all of which cause dilated cardiomyopathy with congestive heart failure in patients.1,2,4 In the cardiomyopathic hamster, a δ-sarcoglycan deletion has been identified as disease-causing, and targeted deletion of the muscle LIM protein (MLP) in mice results in a dilated cardiomyopathy …

Cardiac angiotensin AT2 receptor: what exactly does it do?