Plasma cardiotrophin-1 is elevated in human hypertension and stimulated by ventricular stretch

Pemberton, Chris J.; Raudsepp, Sara D; Yandle, Tim G.; Cameron, Vicky A.; Richards, A. Mark

doi:10.1016/j.cardiores.2005.05.014

Cited by 65 publications

(72 citation statements)

References 42 publications

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“…1992) and B‐type (Pemberton et al . 2005) peptides decreased after the initial increase caused by the mechanical stretch in spite of a constant stimulus. Again, to us this indicates that excretion cannot continue in fatigued heart (in which the oxygen tension gradient is much diminished and oxygen consumption of the cells decreased).…”

Section: Discussionmentioning

confidence: 93%

Hypoxia exposure and B‐type natriuretic peptide release from Langendorff heart of rats

et al. 2016

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AimWe studied whether available oxygen without induced mechanical stretch regulates the release of the biologically active B‐type natriuretic peptide (BNP) from Langendorff heart.MethodsRat hearts were isolated and perfused with a physiological Krebs–Henseleit solution at a constant hydrostatic pressure in Langendorff set‐up. The basal O2 level of perfusate (24.4 ± 0.04 mg L−1) was gradually lowered to 3.0 ± 0.01 mg L−1 over 20 min using N2 gas (n = 7). BNP and O2 level were measured from coronary flow. During control perfusions (n = 5), the O2 concentration was kept at 26.6 ± 0.3 mg L−1.ResultsA low oxygen concentration in the perfusate was associated with a significant increase in BNP release (F = 40.4, P < 0.001). Heart rate decreased when the oxygen concentration in the perfusate reached 9.1 ± 0.02 mg L−1 and continued to fall in lower oxygen concentrations (F = 14.8, P < 0.001). There was also a significant but inverse correlation between BNP and oxygen in the coronary flow (R 2 = 0.27, P < 0.001).ConclusionIn the spontaneously beating Langendorff rat heart, a decreasing concentration of oxygen in the ingoing perfusion increased the secretion of BNP. The effect of oxygen was independent of mechanical stretch of the heart as it occurred even when the heart rate decreased but the pressure conditions remained constant. The difference in the oxygen capacitance of blood and Krebs–Henseleit solution appears to be a major factor affecting secretion of BNP, which is correlated with the oxygen tension of myocardial cells and affected both by the oxygen concentration and capacitance of solution perfusing the heart and by the coronary flow.

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Section: Discussionmentioning

confidence: 93%

Hypoxia exposure and B‐type natriuretic peptide release from Langendorff heart of rats

et al. 2016

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“…Present findings in Wistar adult cells reinforce conceit that the cell growth induced by CT-1 in normal cardiomyocytes resembles volume overload hypertrophy. However, recent experimental [5,14] and clinical [5,6] evidence indicates that CT-1 may be involved in hypertensive LVH. Our ex vivo data show for the first time a temporal association between the increase in myocardial CT-1 expression (mRNA and protein) and cardiomyocyte widening during the development of concentric LVH in SHR, reinforcing a role for this cytokine in hypertrophy that accounts in genetic hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…At cellular level, the growth of cardiomyocytes is the main determinant of LVH, although other factors such as exaggerated collagen accumulation are also involved [2,3]. Recent experimental and clinical evidence indicates that interleukin-6-related cytokines may participate in the development of hypertensive LVH [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…First, intraperitoneal administration of recombinant CT-1 to normotensive mice increases left ventricle weight in a dose-dependent manner, although the geometric pattern of hypertrophy has not been determined [13]. Moreover, left ventricular CT-1 expression is increased in different experimental models of hypertensive LVH [5,14]. In addition, an association between LVH and high plasma levels of CT-1 has recently been observed in essential hypertensive patients [6].…”

Section: Introductionmentioning

confidence: 99%

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Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

López

Dı́ez

Fortuño

2006

Journal of Molecular and Cellular Cardiology

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Cardiotrophin-1 (CT-1) produces longitudinal elongation of neonatal cardiomyocytes, but its effects in adult cardiomyocytes are not known. Recent observations indicate that CT-1 may be involved in pressure overload left ventricular hypertrophy (LVH). We investigated whether the hypertrophic effects of CT-1 are different in cardiomyocytes isolated from adult normotensive and spontaneously hypertensive rats (SHR). Hypertrophy was evaluated by planimetry and confocal microscopy, contractile proteins were quantified by Western blotting and real-time RT-PCR, and intracellular pathways were analyzed with specific chemical inhibitors. CT-1 increased c-fos and ANP expression (p < 0.01) and cell area (p < 0.01) in cardiomyocytes from both rat strains. In Wistar cells, CT-1 augmented cell length (p < 0.01) but did not modify either the transverse diameter or cell depth. In SHR cells, CT-1 increased cell length (p < 0.05), cell width (p < 0.01) and cell depth, augmented the expression of myosin light chain-2v (MLC-2v) and skeletal α-actin (p < 0.01) and enhanced MLC-2v phosphorylation (p < 0.01). The blockade of gp130 or LIFR abolished CT-1-induced growth in the two cell types. All distinct effects observed in cardiomyocytes from SHR were mediated by STAT3. Baseline angiotensinogen expression was higher in SHR cells, and CT-1 induced a 1.7-fold and 3.2-fold increase of angiotensinogen mRNA in cardiomyocytes from Wistar rats and SHR respectively. In addition, AT1 blockade inhibited the specific effects of CT-1 in SHR cells. Finally, ex vivo determinations revealed that adult SHR exhibited enhanced myocardial CT-1 (mRNA and protein, p < 0.01), increased cell width (p < 0.01) and concentric LVH compared with pre-hypertensive SHR. These findings reveal a specific cell-broadening effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive phenotype of these cells may influence the hypertrophic effects of CT-1, probably by means of an exaggerated induction of angiotensinogen expression. We suggest that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with the renin-angiotensin system.

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“…In principle, hemodynamic overload seems to be a sufficient stimulus for the upregulation of LIF and CT-1 expression in the adult human heart. Indeed, the release of CT-1 was found to be stimulated by ventricular stretch [109]. Comparable to systemic levels, the increase in local myocardial CT-1 in hypertensive patients [40,86,126] as well as in patients with dilative cardiomyopathy is furthermore significantly correlated with the left ventricular mass index, suggesting that CT-1 might play a role in structural left ventricular remodeling in these patients [149].…”

Section: General Overview On Gp130 Signalingmentioning

confidence: 95%

Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis

2007

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■ Abstract Circulating levels of interleukin (IL)-6 and related cytokines are elevated in patients with congestive heart failure and after myocardial infarction. Serum IL-6 concentrations are related to decreasing functional status of these patients and provide important prognostic information. Moreover, in the failing human heart, multiple components of the IL-6-glycoprotein (gp)130 receptor system are impaired, implicating an important role of this system in cardiac pathophysiology.Experimental studies have shown that the common receptor subunit of IL-6 cytokines is phosphorylated in response to pressure overload and myocardial infarction and that it subsequently activates at least three different downstream signaling pathways, the signal transducers and activators of transcription 1 and 3 (STAT1/3), the Src-homology tyrosine phosphatase 2 (SHP2)-Ras-ERK, and the PI3K-Akt system. Gp130 receptor mediated signaling promotes cardiomyocyte survival, induces hypertrophy, modulates cardiac extracellular matrix and cardiac function. In this regard, the gp130 receptor system and its main downstream mediator STAT3 play a key role in cardioprotection.This review summarizes the current knowledge of IL-6 cytokines, gp130 receptor and STAT3 signaling in the heart exposed to physiological (aging, pregnancy) and pathophysiological stress (ischemia, pressure overload, inflammation and cardiotoxic agents) with a special focus on the potential role of individual IL-6 cytokines.

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Plasma cardiotrophin-1 is elevated in human hypertension and stimulated by ventricular stretch

Cited by 65 publications

References 42 publications

Hypoxia exposure and B‐type natriuretic peptide release from Langendorff heart of rats

Hypoxia exposure and B‐type natriuretic peptide release from Langendorff heart of rats

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis

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