Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction

Xie, Jun; Wang, Jingjing; Li, Ruotian; Dai, Qing; Yong, Yonghong; Zong, Bing; Yang, Xu; Li, Erguang; Ferro, Albert; Xu, Biao

doi:10.1016/j.yjmcc.2012.04.014

Cited by 37 publications

(36 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[101][102][103][104] Thus, when studying the function of syndecans in disease, the picture is is likely to increase levels of shedding, was found to be protective in rat hearts post-MI. 207 Our findings in Paper II are the first to shed light on the functional effects of increased syndecan-4 shedding in the heart, indicating that during an acute inflammatory response, the increased shedding of syndecan-4 represents a protective mechanism that mitigates cardiac dysfunction and ensures a properly coordinated immune response by promoting recruitment of immune cells. Our findings indicate that ADAMTS1, ADAMTS4 and MMP9 might regulate cardiac syndecan-4 shedding, however experiments using specific inhibitors, siRNA or KO mice for these sheddase should be carried out to determine their roles.…”

Section: Syndecan-4 Shedding In Cardiac Inflammation: Regulation Conmentioning

confidence: 72%

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

et al. 2013

View full text Add to dashboard Cite

Sustained pressure overload induces heart failure, the main cause of mortality in the Western world. Increased understanding of the underlying molecular mechanisms is essential to improve heart failure treatment. Despite important functions in other tissues, cardiac proteoglycans have received little attention. Syndecan‐4, a transmembrane heparan sulfate proteoglycan, is essential for pathological remodeling, and we here investigated its expression and shedding during heart failure. Pressure overload induced by aortic banding for 24 h and 1 week in mice increased syndecan‐4 mRNA, which correlated with mRNA of inflammatory cytokines. In cardiac myocytes and fibroblasts, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide through the toll‐like receptor‐4, induced syndecan‐4 mRNA. Bioinformatical and mutational analyses in HEK293 cells identified a functional site for the proinflammatory nuclear factor‐κB transcription factor in the syndecan‐4 promoter, and nuclear factor‐κB regulated syndecan‐4 mRNA in cardiac cells. Interestingly, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide induced nuclear factor‐κB‐dependent shedding of the syndecan‐4 ectodomain from cardiac cells. Overexpression of syndecan‐4 with mutated enzyme‐interacting domains suggested enzyme‐dependent heparan sulfate chains to regulate shedding. In cardiac fibroblasts, lipopolysaccharide reduced focal adhesion assembly, shown by immunohistochemistry, suggesting that inflammation‐induced shedding affects function. After aortic banding, a time‐dependent cardiac recruitment of T lymphocytes was observed by measuring CD3, CD4 and CD8 mRNA, which was reduced in syndecan‐4 knockout hearts. Finally, syndecan‐4 mRNA and shedding were upregulated in failing human hearts. Conclusively, our data suggest that syndecan‐4 plays an important role in the immune response of the heart to increased pressure, influencing cardiac remodeling and failure progression.

show abstract

Section: Syndecan-4 Shedding In Cardiac Inflammation: Regulation Conmentioning

confidence: 72%

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

et al. 2013

View full text Add to dashboard Cite

show abstract

“…30 Overexpressing syndecan-4 with an adenoviral vector in a rat MI model further supports the protective role of this proteoglycan, possibly mediated by inducing angiogenesis and by inhibiting inflammation and fibrosis. 94 Whereas, the overexpression of syndecan-4 ectodomain seems to be deleterious. As mentioned previously, overexpressing the extracellular domain of syndecan-4 impairs cardiac function and increases cardiac rupture after MI by impairing granulation tissue formation.…”

Section: Cell Surface Proteoglycans: Syndecansmentioning

confidence: 99%

Myocardial Extracellular Matrix

Rienks

Papageorgiou

Frangogiannis

et al. 2014

Circulation Research

309

170

View full text Add to dashboard Cite

Abstract:The cardiac extracellular matrix (ECM) is a complex architectural network consisting of structural and nonstructural proteins, creating strength and plasticity. The nonstructural compartment of the ECM houses a variety of proteins, which are vital for ECM plasticity, and can be divided into 3 major groups: glycoproteins, proteoglycans, and glycosaminoglycans. The common denominator for these groups is glycosylation, which refers to the decoration of proteins or lipids with sugars. This review will discuss the fundamental role of the matrix in cardiac development, homeostasis, and remodeling, from a glycobiology point of view. Glycoproteins (eg, thrombospondins, secreted protein acidic and rich in cysteine, tenascins), proteoglycans (eg, versican, syndecans, biglycan), and glycosaminoglycans (eg, hyaluronan, heparan sulfate) are upregulated on cardiac injury and regulate key processes in the remodeling myocardium such as inflammation, fibrosis, and angiogenesis. Albeit some parallels can be made regarding the processes these proteins are involved in, their specific functions are extremely diverse. In fact, under varying conditions, individual proteins can even have opposing functions, making spatiotemporal contribution of these proteins in the rearrangement of multifaceted ECM very hard to grasp. Alterations of protein characteristics by the addition of sugars may explain the immense, yet tightly regulated, variability of the remodeling cardiac matrix. Understanding the role of glycosylation in altering the ultimate function of glycoproteins, proteoglycans, and glycosaminoglycans in the myocardium may lead to the development of new biochemical structures or compounds with great therapeutic potential for patients with heart disease. (Circ Res. 2014;114:872-888.)

show abstract

“…Moreover, synd4 could initiate its downstream pathway via protein kinase Cα (PKCα) (11), which seems to be required for cardiac adaptations to several stimulations (12). Our previous report (13) and works of other authors (14,15) have indicated that synd4 takes part in cardiac hypertrophy as an adaptation in the myocardium infarction model and the transverse aortic constriction (TAC) model. Calcineurin-NFAT pathway is identified as downstream signaling of synd4 in pathological cardiac hypertrophy.…”

Section: Primary Culture Of Neonatal Mice Ventricular Cardiomyocytes mentioning

confidence: 98%

“…Recombinant adenoviruses for gene delivery were prepared using the pAd-Easy system, as described previously (13). A cDNA corresponding to the coding region of human syndecan-4 (NM_002999) was subcloned into pShuttle-CMV.…”

Section: Construction and Preparation Of Recombinant Adenovirusesmentioning

confidence: 99%

See 1 more Smart Citation

Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

Xie

Chen

et al. 2016

Mol Med

Self Cite

View full text Add to dashboard Cite

Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4 -/-) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4 -/-compared with wildtype (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy.

show abstract

Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction

Cited by 37 publications

References 39 publications

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

Myocardial Extracellular Matrix

Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

Contact Info

Product

Resources

About