Insights into pathogenesis and treatment of cytokines in cardiomyopathy

Vadlamani, Lou; Abraham, William T.

doi:10.1007/s11886-000-0008-3

Cited by 9 publications

(5 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also interesting that the increase in cardiac damage and apoptosis cell death in the absence of a functional iNOS gene was associated with alteration of the kinetics of cytokine production. Production of TNF-␣ and IL-6, which have been implicated in promoting myocyte death and heart failure disease progression after infarction (44), was increased significantly at earlier time points of reperfusion in iNOS Ϫ/Ϫ mice compared with lower levels of wild-type animals.…”

Section: Induction Of No Synthesis Reduces Cell Death By Apoptosismentioning

confidence: 91%

Absence of inducible nitric oxide synthase modulates early reperfusion‐induced NF‐κB and AP‐1 activation and enhances myocardial damage

et al. 2002

View full text Add to dashboard Cite

The role of nitric oxide (NO) generated by the inducible NO synthase (iNOS) during myocardial ischemia and reperfusion is not understood. We investigated the role of iNOS during early reperfusion damage induced in genetically deficient iNOS (iNOS-/-) mice and wild-type littermates. In wild-type mice, ischemia (60 min) and reperfusion (60 min) induced an elevation in serum levels of creatine phosphokinase and myocardial injury characterized by the presence of scattered apoptotic myocytes and mild neutrophil infiltration. Northern blot analysis showed increased expression of iNOS, whose activity was markedly elevated after reperfusion. Immunohistochemistry showed staining for nitrotyrosine; Western blot analysis showed elevated expression of heat shock protein 70 (HSP70), a putative cardioprotective mediator. Plasma levels of nitrite and nitrate, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-10 were also increased. These events were preceded by degradation of inhibitor kappaBalpha (IkappaBalpha), activation of IkappaB kinase complex (IKK) and c-Jun-NH2-terminal kinase (JNK), and subsequently activation of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) as early as 15 min after reperfusion. In contrast, iNOS-/- mice experienced 35% mortality after reperfusion. The extensive myocardial injury was associated with marked apoptosis and infiltration of neutrophils whereas expression of HSP70 was less pronounced. Nitrotyrosine formation and plasma levels of nitrite and nitrate were undetectable. TNF-alpha and IL-6 were increased and IL-10 was reduced in earlier stages of reperfusion. Activation of IKK and JNK and binding activity of NF-kappaB and AP-1 were significantly reduced. Thus, we conclude that iNOS plays a beneficial role in modulating the early defensive inflammatory response against reperfusion injury through regulation of signal transduction.

show abstract

Section: Induction Of No Synthesis Reduces Cell Death By Apoptosismentioning

confidence: 91%

Absence of inducible nitric oxide synthase modulates early reperfusion‐induced NF‐κB and AP‐1 activation and enhances myocardial damage

et al. 2002

View full text Add to dashboard Cite

show abstract

“…1,[3][4][5][6] Among the earliest events during ischemia-induced ventricular dysfunction, the renin-angiotensin system and secretion of atrial natriuretic peptide (ANP) are activated. 7,8 In addition, in the endothelin system, 9,10 cytokines such as IL-1, IL-6, and tumor necrosis factor-␣, [11][12][13][14] stress-proteins, 15 and anti-oxidants 16 change their expression pattern. However, these changes generally are not characteristic for ICM.…”

mentioning

confidence: 99%

NCAM(CD56) and RUNX1(AML1) Are Up-Regulated in Human Ischemic Cardiomyopathy and a Rat Model of Chronic Cardiac Ischemia

Gattenlöhner

Waller

Ertl

et al. 2003

The American Journal of Pathology

View full text Add to dashboard Cite

Chronic myocardial ischemia is the leading cause of impaired myocardial contractility and heart failure. To identify differentially expressed genes in human ischemic cardiomyopathy (ICM), we constructed a subtracted cDNA library using specimens of ICM compared to normal human heart. Among 100 randomly sequenced clones, seven sequences represented recently identified candidate genes for differential expression in cardiac hypertrophy. A further clone without a known hypertrophy-association coded for the adhesion molecule NCAM(CD56). RNase protection assay, immunohistochemistry, and Western blotting revealed strong overexpression of NCAM(CD56) in all hearts with ICM (n ‫؍‬ 14) compared to normal hearts (n ‫؍‬ 8), whereas in congestive cardiomyopathy (CCM) (n ‫؍‬ 8), hypertrophic obstructive cardiomyopathy (n ‫؍‬ 2), myocarditis (n ‫؍‬ 4), and sarcoidosis (n ‫؍‬ 2), at most slight overexpression of NCAM(CD56) was observed. NCAM(CD56) overexpression abnormally involved the whole cell membrane and the cytoplasma of cardiomyocytes only inside and adjacent to ischemia-induced cardiac scars. Normal or hypertrophic fibers at a distance from ischemic scars were devoid of NCAM overexpression. Identical alterations were observed in an experimental rat ICM model, but not in normal nor in spontaneously hypertensive rat hearts. The most common cause of chronic heart failure is coronary artery disease (CAD), which results in left ventricular dysfunction.

show abstract

“…Furthermore, inflammatory response is also a important pathological feature of cardiomyopathy [ 32 ]. Pro-inflammatory cytokines IL-6 and TNF-α appear to make a significant contribution to the pathophysiology of cardiomyopathy and heart failure [ 33 ]. In contrast to pro-inflammatory mediators, anti-inflammatory cytokine IL-10 influences the inflammatory activation of monocytes [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Transplantation of umbilical cord blood-derived mesenchymal stem cells as therapy for adriamycin induced-cardiomyopathy

Zhang¹,

Zhang²,

Yang³

et al. 2022

Bioengineered

View full text Add to dashboard Cite

Umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) have been reported to possess cardioprotective effects in diseases. However, its effects on cardiomyopathy remain unclear. This study aimed to the therapeutic effects of UCBMSC transplantation on adriamycin (ADR)-induced cardiomyopathy. UCBMSCs isolated from human UCB were identified by detecting surface markers (CD29, CD90, CD34, and CD45) using flow cytometry. The effect of UCBMSCs on left ventricular end-diastolic dimension (LVEDD), left ventricular systolic end-diastolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fraction shortening (LVFS) were determined by echocardiography. Histological changes were observed by HE and Masson staining. The serum levels of collagen-I (Col-I), brain natriuretic peptide (BNP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB, interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) were measured by corresponding kits. The protein levels of IL-6, IL-10, and TNF-α were measured by Western blotting. The isolated UCBMSCs manifested the positive expression of CD29 and CD90, and the negative expression of CD34 and CD45. UCBMSC transplantation significantly reduced LVEDD and LVESD, and increased LVEF and LVFS in ADR-induced cardiomyopathy model rats. Cardiac injury and high collagen deposition in model rats were alleviated by UCBMSC treatment. Moreover, UCBMSCs decreased the serum levels of Col-I, BNP, AST, LDH, CK, CK-MB, IL-6, IL-10, and TNF-α in model rats. Overall, UCBMSCs exert the therapeutic effects on ADR-induced cardiomyopathy through recovering the myocadiac function and alleviating the inflammatory response.

show abstract

Insights into pathogenesis and treatment of cytokines in cardiomyopathy

Cited by 9 publications

References 92 publications

Absence of inducible nitric oxide synthase modulates early reperfusion‐induced NF‐κB and AP‐1 activation and enhances myocardial damage

Absence of inducible nitric oxide synthase modulates early reperfusion‐induced NF‐κB and AP‐1 activation and enhances myocardial damage

NCAM(CD56) and RUNX1(AML1) Are Up-Regulated in Human Ischemic Cardiomyopathy and a Rat Model of Chronic Cardiac Ischemia

Transplantation of umbilical cord blood-derived mesenchymal stem cells as therapy for adriamycin induced-cardiomyopathy

Contact Info

Product

Resources

About