Serum depletion induces cell loss of rat cardiac fibroblasts and increased expression of extracellular matrix proteins in surviving cells

Leicht, Monika; Briest, Wilfried; Hölzl, Alexander; Zimmer, Heinz‐Gerd

doi:10.1016/s0008-6363(01)00391-1

Cited by 31 publications

(23 citation statements)

References 45 publications

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“…The NE concentration and the induction time for apoptosis in these studies were similar to the findings in ours using CF. In a previous study, Leicht et al observed that serum withdrawal could lead to a 36% cell loss in CF due to necrosis [20]. However in our study, the significant increase in apoptotic cell percentage did not due to serum withdrawal but NE induction.…”

Section: Discussioncontrasting

confidence: 80%

“…Conversely, there are situations where CF can undergo programmed cell death. Stimulants including angiotensin II modulated nitricoxide production [16], osmotic stress [18], osteopontindeficiency, interleukin-1β-induced nitric-oxide production [19] and serum-free condition [20] can induce apoptosis and necrosis in CF. It is important for the heart to maintain a balance population of myocytes and non-myocytes.…”

Section: Discussionmentioning

confidence: 99%

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High dose norepinephrine-induced apoptosis in cultured rat cardiac fibroblast

Lai

Sanderson

2009

International Journal of Cardiology

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Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

High dose norepinephrine-induced apoptosis in cultured rat cardiac fibroblast

Lai

Sanderson

2009

International Journal of Cardiology

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“…First, because MMP-2 release even in controls gradually increased time-dependently, the culturing conditions may partly offset the difference in MMP-2 abundance between BNP-treated cell cultures and controls. Supporting this hypothesis, a study by Leicht et al 42 showed that serum depletion increased the MMP activity in rat CFs. Second, high concentrations of BNP were needed in this cell culture system to increase intracellular cGMP.…”

Section: Discussionmentioning

confidence: 85%

Brain Natriuretic Peptide Is Produced in Cardiac Fibroblasts and Induces Matrix Metalloproteinases

Tsuruda

Boerrigter

Huntley

et al. 2002

Circulation Research

269

195

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Abstract-Cardiac fibroblasts (CFs) produce extracellular matrix proteins and participate in the remodeling of the heart.It is unknown if brain natriuretic peptide (BNP) is synthesized by CFs and if BNP participates in the regulation of extracellular matrix turnover. In this study, we examined the production of BNP in adult canine CFs and the role of BNP and its signaling system on collagen synthesis and on the activation of matrix metalloproteinases (MMPs Key Words: cardiac fibroblasts Ⅲ extracellular matrix Ⅲ remodeling Ⅲ cGMP Ⅲ protein kinase G T he cardiac interstitium is a dynamic structure, as reflected by continuous synthesis and degradation of matrix proteins. The family of matrix metalloproteinases (MMPs) consists of more than 20 different zinc-containing, Ca 2ϩ -dependent endopeptidases. 1,2 They degrade matrix proteins and therefore play an important role in the physiological regulation of the interstitium. The interstitial collagenases (MMP-1 and MMP-13), the stromelysin (MMP-3), the gelatinases (MMP-2 and MMP-9), and membranous-type 1 MMPs (MMP-14; MT1-MMP) have been demonstrated within the mammalian myocardium. 2 Furthermore, dysregulation of MMP proteins and their endogenous inhibitor, tissue inhibitors of MMP (TIMP), has been observed in the hypertensive and the failing heart, suggesting an important role of MMP in the process of ventricular remodeling. [3][4][5][6][7] Cardiac fibroblasts (CFs) play a crucial role in the regulation of the extracellular matrix (ECM) of the heart by synthesizing collagen and other matrix proteins as well as promoting their degradation by secreting MMP proteins. In response to myocardial injury, activation of CFs occurs. These activated CFs (myofibroblasts) have special morphological and functional characteristics. 8,9 The natriuretic peptides (NPs) atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) play important roles in maintaining cardiorenal homeostasis under physiological and pathological conditions. 10 ANP and BNP are synthesized by cardiomyocytes, and their production is stimulated in pathologic conditions such as myocardial infarction (MI), cardiac hypertrophy, and heart failure (HF). 11-13 ANP and BNP have natriuretic, vasodilating, and lusitropic properties, and they inhibit the sympathetic and renin-angiotensin-aldosterone system. 14,15 These actions are primarily mediated by the second messenger cGMP. 16 Cameron et al 17 have recently reported that ANP is produced in CFs after MI, indicating that fibroblasts, like cardiomyocytes, can be a source of NPs. However, it remains unknown if BNP is produced by CFs.Although it is well established that BNP has growthinhibiting properties in the heart, 18 -21 the role of BNP on the regulation of the cardiac interstitium remains undefined. Given the widespread cross-talk of the NPs with other systems that are activated in cardiorenal disorders, we aimed to investigate whether CFs are a source of BNP and whether BNP and its signaling system contribute to the regulation of Original

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“…3 and 4). Transcriptional regulation of TIMPs is mediated by cytokines and phorbol esters (Leicht et al, 2001). Although we did not examine the details for effects of IR positive on MMPs and negative on TIMP-4, the changes seemed to be governed by ERK after EPO treatment (Figs.…”

Section: Discussionmentioning

confidence: 96%