Abstract：
:Pulmonary arterial hypertension (PAH) is a complex disease that causes significant morbidity and mortality and is clinically characterized by an increase in pulmonary vascular resistance. The histopathology is marked by vascular proliferation/fibrosis, remodeling, and vessel obstruction. Development of PAH involves the complex interaction of multiple vascular effectors at all anatomic levels of the arterial wall. Subsequent vasoconstriction, thrombosis, and inflammation ensue, leading to vessel wall remodeling and cellular hyperproliferation as the hallmarks of severe disease. These processes are influenced by genetic predisposition as well as diverse endogenous and exogenous stimuli. Recent studies have provided a glimpse at certain molecular pathways that contribute to pathogenesis; these have led to the identification of attractive targets for therapeutic intervention. We will review our current understanding of the mechanistic underpinnings of the genetic and exogenous/acquired triggers of PAH. The resulting imbalance of vascular effectors provoking pathogenic vascular changes will also be discussed, with an emphasis on common and overarching regulatory pathways that may relate to the primary triggers of disease. The current conceptual framework should allow for future studies to refine our understanding of the molecular pathogenesis of PAH and improve the therapeutic regimen for this disease.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Chan SY,Loscalzo Jdoi
10.1016/j.yjmcc.2007.09.006subject
Has Abstractpub_date
2008-01-01 00:00:00pages
14-30issue
1eissn
0022-2828issn
1095-8584pii
S0022-2828(07)01237-0journal_volume
44pub_type
杂志文章,评审abstract：:We have tested the hypothesis that thyroid state may influence both the flow of cellular Ca2+ and the myofilament response to Ca2+ by effects on intracellular pH (pHi) and Na+ (Nai+). Single cardiac myocytes isolated from hypothyroid, euthyroid and hyperthyroid animals were loaded with fura-2/AM (Cai2+ probe), BCECF/A...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1997.0495
更新日期：1997-10-01 00:00:00
abstract：:This study examined the potential role of ET-1 and the contribution of protein kinase C (PKC) in the desensitization of the ET-1 transmembrane signaling pathway in the left circumflex coronary artery (CCA) of a dog model of congestive heart failure (CHF). In the CCA of the rapid ventricular pacing-overdrive dog model ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1993.1102
更新日期：1993-08-01 00:00:00
abstract：:Chronic kidney disease (CKD) is a significant risk factor for cardiovascular and peripheral vascular disease. Although mesenchymal stem cell (MSC)-based therapy is a promising strategy for treatment of ischemic diseases associated with CKD, the associated pathophysiological conditions lead to low survival and prolifer...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2016.05.011
更新日期：2016-08-01 00:00:00
abstract：:Cardiocyte loss during myocardial hypertrophy leads to progressive dysfunction in human hearts with chronic hemodynamic overload. The mechanism for such cell elimination is unknown. We examined lysosomal participation in cardiocytic degradation present in human cardiac biopsies, utilizing electron microscopic cytochem...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1999.1064
更新日期：2000-01-01 00:00:00
abstract：:We previously established a new measuring method of the myocardial O2 consumption of mechanically unloaded rat left-ventricular slices. O 2 consumption of unstimulated myocardium corresponds to basal metabolism. We have found O2 consumption of stimulated myocardium to include basal metabolism and O 2 consumption for C...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1997.0630
更新日期：1998-03-01 00:00:00
abstract：:Interactions between platelets with injured vascular endothelium contribute to thrombotic occlusion. A murine monoclonal antibody [7E3 F(ab')2] to the platelet GPIIb/IIIa receptor complex was used to inhibit platelet aggregation in an experimental model of coronary artery thrombosis. Prevention of thrombotic occlusion...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(89)90650-0
更新日期：1989-04-01 00:00:00
abstract：:Inflammation is critical in the pathobiology of atherosclerosis. An essential player in the inflammatory process in atherosclerosis are macrophages that scavenge oxidatively modified low-density lipoproteins (OxLDL) deposited in the subendothelium of systemic arteries that secrete a myriad of pro-inflammatory mediator...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.11.006
更新日期：2019-01-01 00:00:00
abstract：BACKGROUND:Cultured adult mouse and rat cardiomyocytes are the best and low-cost cell model for cardiac cellular physiology, pathology, drug toxicity screening, and intervention. The functions of mouse cardiomyocytes decline faster than rat cardiomyocytes in culture conditions. However, little is known about the differ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2019.09.006
更新日期：2019-11-01 00:00:00
abstract：:Chronic pressure overload to the heart leads to cardiac hypertrophy and failure through processes that involve reorganization of subcellular compartments and alteration of established signaling mechanisms. To identify proteins contributing to this process, we examined changes in nuclear-associated myofilament proteins...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2010.02.009
更新日期：2010-06-01 00:00:00
abstract：:Rapamycin (Sirolimus®) is used to prevent rejection of transplanted organs and coronary restenosis. We reported that rapamycin induced cardioprotection against ischemia-reperfusion (I/R) injury through opening of mitochondrial K(ATP) channels. However, signaling mechanisms in rapamycin-induced cardioprotection are cur...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2012.09.007
更新日期：2012-12-01 00:00:00
abstract：:Disturbances of cellular calcium homeostasis due to oxidative stress are involved in reperfusion associated phenomena like myocardial stunning and reperfusion induced arrhythmias. This study investigates the effect of the major neutrophil-derived oxidant hypochlorous acid (HOCl) on the l-type calcium current (ICa,L) o...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0749
更新日期：1998-09-01 00:00:00
abstract：BACKGROUND:Statins have been shown to increase the level of circulating progenitor cells in peripheral blood supposedly due to a mobilization of progenitor cells from the bone marrow niche. Osteoclast/osteoblast interaction has been associated with progenitor cell mobilization. Here, we investigated the role of statins...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2012.12.018
更新日期：2013-04-01 00:00:00
abstract：BACKGROUND:Inflammatory serine proteases (ISPs) play an important role in cardiac repair after injury through hydrolysis of dead cells and extracellular matrix (ECM) debris. Evidence also suggests an important role of ISPs in the coordination of the inflammatory response. However, the effect of ISPs on inflammation is ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2019.06.016
更新日期：2019-09-01 00:00:00
abstract：:The effects of cytochalasin D, a specific F-actin depolymerizing agent, on Ca2+ transients in rat ventricular cardiomyocytes were investigated. Cytochalasin D (20 microM) significantly slowed decay of Ca2+ transients (tau decay control cells=28.1+/-1.3, n=28tau decay=47.3+/-2.8 ms, n=20, P<0.001). The rising phase of ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1998.0715
更新日期：1998-08-01 00:00:00
abstract：:Myocardial ischemia is associated with accumulation of lyso-phospholipids, including lyso-platelet activating factor, the degradation product and precursor of platelet activating factor. These compounds produce cellular and microvascular damage and, in the myocardium, depression of contractility and arrhythmia. The po...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(92)91048-a
更新日期：1992-06-01 00:00:00
abstract：:We made novel measurements of the influence of rest intervals and stimulation frequency on twitch contractions and on sarcoplasmic reticulum (SR) Ca(2+)-content (using rapid cooling contractures, RCCs) in isolated ventricular muscle strips from rat and rabbit hearts at a physiological temperature of 37 degrees C. In a...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2000.1252
更新日期：2000-12-01 00:00:00
abstract：:Oxidative stress markedly alters protein function through redox modification of sulfhydryl groups present in cysteine residues. To explore the role of redox state in modulating cardiac K+ channels, this study examined the effects of sulfhydryl modifiers on the repolarizing transient outward current (Ito) in voltage-cl...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2002.2112
更新日期：2002-12-01 00:00:00
abstract：RATIONALE:Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH). OBJECTIVE:We aimed to investigate the effect of sEH inhibition in at...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2016.08.001
更新日期：2016-09-01 00:00:00
abstract：:Cardiac tyhrotropin-releasing hormone (TRH) is overexpressed in the hypertrophied left ventricle (LV) of spontaneously hypertensive rats (SHR) and its inhibition prevents both hypertrophy and fibrosis. In a normal heart, the TRH increase induces fibrosis and hypertrophy opening the question of whether TRH could be a c...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2018.09.009
更新日期：2018-11-01 00:00:00
abstract：:Oxygen deprivation for prolonged periods leads to cardiac cell death and ventricular dysfunction. The ability to prevent myocardial cell death would be of significant therapeutic value in maintaining cardiac function after injury. While caspases have been suggested to play a critical role in apoptosis, their involveme...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1999.1057
更新日期：2000-01-01 00:00:00
abstract：:Cardiac ventricular responsiveness to serotonin appears in rat postinfarction congestive heart failure (CHF), mainly mediated by 5-HT(4) receptors in chronic dilated CHF and 5-HT(2A) receptors in acute CHF. To differentiate between the effects of left ventricular (LV) hypertrophy and failure on 5-HT(2A)- and 5-HT(4)-m...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2007.08.019
更新日期：2007-12-01 00:00:00
abstract：:Since ascorbate is unnecessary for cell growth and survival, cardiac fibroblasts are routinely cultured without it. However, ascorbate is necessary for optimal collagen synthesis, so we hypothesized that its presence would influence cell phenotype. Cardiac fibroblasts cultured without ascorbate had increased intracell...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2017.09.005
更新日期：2017-12-01 00:00:00
abstract：BACKGROUND:Dilated cardiomyopathy (DCM) could be caused by mutations in more than 40 different genes. However, the pathogenic impact of specific mutations is in most cases unknown complicating the genetic counseling of affected families. Therefore, functional studies could contribute to distinguish pathogenic mutations...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2015.12.015
更新日期：2016-02-01 00:00:00
abstract：:In view of considerable gaps in our knowledge of myocardial peroxisomes. the aim of the present study is, on the basis of extensive electron-microscopic investigations, to provide reliable results on the inducibility of a proliferation (increase in the number) of these organelles in rodents' heart by several agents an...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0260
更新日期：1997-01-01 00:00:00
abstract：:Pyroptosis is a pro-inflammatory form of programmed cell death, whose genesis directly depended on caspase-1 activation. Pulmonary hypertension (PH) is a disease characterized, in part, by vascular fibrosis. Up to now, there is no report on the relationship between pyroptosis and vascular fibrosis in PH. Here, we conf...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2019.10.008
更新日期：2020-01-01 00:00:00
abstract：:Doxorubicin (Dox) is a widely used antineoplastic agent. Irreversible cardiomyopathy is a serious and dose-limiting side effect after chronic administration. The iron chelating bispiperazinedione ICRF-187 is currently the only drug which affords protection against Dox-induced cardiotoxicity. To compare the protective ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1994.1136
更新日期：1994-09-01 00:00:00
abstract：:Endothelin-1 (ET-1) is a potent agonist of cell growth that also stimulates Na(+)/H(+) exchanger isoform 1 (NHE-1) activity. It was hypothesized that the increase in intracellular Na(+) ([Na(+)](i)) mediated by NHE-1 activity may induce the reverse mode of Na(+)/Ca(2+) exchanger (NCX(rev)) increasing intracellular Ca(...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2006.05.016
更新日期：2006-11-01 00:00:00
abstract：:We made acute cardiac failure in excised cross-circulated canine hearts by a new coronary perfusion protocol consisting of Ca2+ free Tyrode perfusion for the first 10 min, high Ca2+ (16 mmol/l) Tyrode perfusion for the next 5 min, and normal Tyrode perfusion for the last 5 min interrupting blood cross circulation. Aft...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/0022-2828(95)90022-5
更新日期：1995-09-01 00:00:00
abstract：:Using the ultrastructural criteria established by Schaper et al. 1979 [27] for distinguishing between different degrees of ischemic change in dog myocardium, slight ischemic changes are observed in the pig suboendocardium as early as 1 min after occlusion of the LAD artery. Moderate change throughout the thickness of ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/s0022-2828(84)80716-6
更新日期：1984-01-01 00:00:00
abstract：:There is currently a growing global burden of valvular heart diseases due to aging populations and changing lifestyles. Valvular heart diseases mainly include the malfunctioning of aortic and mitral valves and are characterized by extensive tissue remodeling, which includes calcification, endothelial dysfunction, and ...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/j.yjmcc.2020.03.015
更新日期：2020-05-01 00:00:00
