Stretch-Induced Upregulation of Connective Tissue Growth Factor in Rabbit Cardiomyocytes

Abstract

Connective Tissue Growth Factor (CTGF, CCN2) is considered to play an important role in cardiac remodelling. We studied whether stretch is a primary stimulus to induce CTGF expression in vivo in rabbit heart, and in vitro in isolated cardiomyocytes and fibroblasts. Twenty weeks of combined volume and pressure overload resulted in eccentric left ventricular (LV) hypertrophy, with increased LV internal diameter (+36 %) and LV weight (+53 %). Myocardial CTGF mRNA and protein levels were substantially increased in the overloaded animals. In isolated adult rabbit cardiomyocytes, cyclic stretch strongly induced CTGF mRNA expression (2.9-fold at 48 h), whereas in cardiac fibroblasts CTGF-induction was transient and modest (1.4-fold after 4 h). Conditioned medium from stretched fibroblasts induced CTGF mRNA expression in non-stretched cardiomyocytes (2.3-fold at 48 h). Our findings indicate that stretch is an important primary trigger for CTGF-induction in the overloaded heart.

Local microRNA‐133a downregulation is associated with hypertrophy in the dyssynchronous heart

“…By contrast, SRF and NFATc4 (both known target genes of miR‐133a) did not show any relation with miR‐133a in this study and are most likely not involved in the hypertrophic response in our model of local hypertrophy. In vitro studies showed that increased CTGF expression in isolated, stretched cardiomyocytes coincided with development of a hypertrophic response 1, 3. Moreover, in a rabbit model of eccentric hypertrophy, where strains and workload are expected to be high throughout the LV wall, CTGF was also found to be overexpressed 3.…”

“…In vitro studies showed that increased CTGF expression in isolated, stretched cardiomyocytes coincided with development of a hypertrophic response 1, 3. Moreover, in a rabbit model of eccentric hypertrophy, where strains and workload are expected to be high throughout the LV wall, CTGF was also found to be overexpressed 3. Of note is that recent studies question the importance of CTGF in cardiac structural remodelling, indicating that while it is an important biomarker of myocardial remodelling, it most likely does not play a decisive role in this process24, 25 …”

“…On the other hand, it has been shown that stretching isolated cardiomyocytes can affect gene expression, increase protein synthesis, and induce hypertrophy 1. Similarly, stretching isolated cardiac fibroblasts increases expression of extracellular matrix (ECM) genes and proteins 2, 3…”

The Effect of Increased Frequency of Hemodialysis on Volume-Related Outcomes: A Secondary Analysis of the Frequent Hemodialysis Network Trials

“…In the Daily Trial, an association was found between change in predialysis SBP over the 12-month study period and change in LVM (slope estimate 6.6 g per 10 mm Hg in the group receiving 3/week HD and 10.1 g per 10 mm Hg in the group assigned to frequent HD) [17] . In the Daily Trial, a reduction in ECF or TIFL could affect LVM indirectly, via a reduction in blood pressure [26] , or volume overload reduction per se might effect a reduction in LVM, since fluid overload during the interdialytic period increases cardiac strain [1][2][3] and subsequently connective tissue growth [27] .…”

A possible relationship between gluconeogenesis and glycogen metabolism in rabbits during myocardial ischemia

“…The cyclophilin A gene was utilized as a reference to normalize the reactions (Blaauw et al 2013), and the cDNA from the control group was used as a calibrator for the assays. The relative expression of the calibrators was assigned a value of 1 unit.…”