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Background: Cardiovascular diseases are the most important cause of death in patients with impaired kidney function. Left ventricular hypertrophy (LVH), cardiac interstitial fibrosis and cardiovascular calcifications are characteristic of chronic renal insufficiency (CRI). Periostin is a fibrogenesis- and calcification-related matricellular protein re-expressed in adult tissues undergoing remodelling in response to pathological stimuli. The role of periostin in CRI-induced LVH is unknown., Methods: Rats were 5/6-nephrectomized (NX), and after 15 weeks of disease progression high-calcium, high-phosphate or paricalcitol treatment was given for 12 weeks. Cardiac tissue and blood samples were taken to study periostin gene expression and to determine factors contributing to its reactivation, respectively. Left ventricular (LV) periostin expression was also examined in response to angiotensin II or arginine(8)-vasopressin (AVP)-induced pressure overload and in spontaneously hypertensive rats., Results: CRI resulted in a 6.5-fold increase in LV periostin messenger RNA (mRNA) levels. Positive extracellular immunostaining for periostin was detected in areas of infiltrated inflammatory cells and fibrotic lesions. There was a significant correlation between LV periostin mRNA levels and plasma biomarkers of impaired kidney function, LVH, fibrogenesis-related proteins osteopontin and osteoactivin, and anti-calcific matrix Gla protein. Moreover, LV periostin gene expression in CRI correlated positively with systolic blood pressure (BP) and was activated rapidly in response to angiotensin II or AVP infusions., Conclusions: Periostin is involved in fibrotic cardiac remodelling in CRI. The re-expression of periostin is localized to the fibrotic and inflammatory lesions and is most likely the consequence of elevated BP.

In this study, we investigated whether local intramyocardial GATA4 overexpression affects the left ventricular (LV) remodelling process and the importance of phosphorylation at serine 105 (S105) for the actions of GATA4 in an angiotensin II (AngII)‐induced hypertension rat model. Adenoviral constructs overexpressing wild‐type GATA4 or GATA4 mutated at S105 were delivered into the anterior LV free wall. AngII (33.3 µg/kg/h) was administered via subcutaneously implanted minipumps. Cardiac function and structure were examined by echocardiography, followed by histological immunostainings of LV sections and gene expression measurements by RT‐qPCR. The effects of GATA4 on cultured neonatal rat ventricular fibroblasts were evaluated. In AngII‐induced hypertension, GATA4 overexpression repressed fibrotic gene expression, reversed the hypertrophic adult‐to‐foetal isoform switch of myofibrillar genes and prevented apoptosis, whereas histological fibrosis was not affected. Overexpression of GATA4 mutated at S105 resulted in LV chamber dilatation, cardiac dysfunction and had minor effects on expression of myocardial remodelling genes. Fibrotic gene expression in cardiac fibroblasts was differently affected by overexpression of wild‐type or mutated GATA4. Our results indicate that GATA4 reduces AngII‐induced responses by interfering with pro‐fibrotic and hypertrophic gene expressions. GATA4 actions on LV remodelling and fibroblasts are dependent on phosphorylation site S105. [ABSTRACT FROM AUTHOR]

The article presents information study which investigated the impact of B-type natriuretic peptide (BNP) on cardiac function. BNP is an endogenous peptide that has natriuretic, diuretic and blood-pressure reducing actions. The study showed that increased intramyocardial BNP gene delivery resulted in an improvement in cardiac function and postinfarction.

Abstract: Parthenolide has shown promise in treatment of various cancers via inhibition of the transcription factor signal transducer and activator of transcription 3 (STAT3). Activation of STAT3 has been observed in left ventricular hypertrophy (LVH); however, its exact role is not known. The aim of the study was to examine the effects of parthenolide on pressure overload-induced LVH in rats. Pressure overload was induced by angiotensin II (Ang II) infusion (33μg/kg/h) for 1 week in the presence or absence of parthenolide (0.5mg/kg/day, i.p.). Ang II infusion resulted in LVH associated with increased phosphorylation of STAT3 at Tyr705 and Ser727. Parthenolide treatment had no effect on ejection fraction, but abolished the activation of STAT3 and reduced the Ang II-induced LVH (LV posterior wall thickness in end-diastole: 2.28±0.12mm vs. 1.80±0.06mm, P <0.001). Importantly, parthenolide treatment had no effect on heart rate or blood pressure. Parthenolide treatment almost completely abolished the Ang II-induced increase in the number of cells positive for prolyl-4-hydroxylase, a marker for collagen-synthesizing cells, as well as Ang II-induced interstitial fibrosis in the left ventricles. This was associated with significant attenuation of Ang II-induced increase in mRNA levels of type 1 collagen and fibronectin. Moreover, parthenolide attenuated the Ang II-induced expression of interleukin-6, a potent pro-hypertrophic fibroblast-derived factor. We conclude that pharmacological inhibition of STAT3 signaling by parthenolide has favorable effects on pressure overload-induced LVH through attenuation of fibroblast activation. Therefore parthenolide may prove as a useful therapy for certain cardiovascular disease. [Copyright &y& Elsevier]