Periostin regulates lysyl oxidase through ERK1/2 MAPK-dependent serum response factor in activated cardiac fibroblasts.

Collagen crosslinking, mediated by lysyl oxidase, is an adaptive mechanism of the cardiac repair process initiated by cardiac fibroblasts postmyocardial injury. However, excessive crosslinking leads to cardiac wall stiffening, which impairs the contractile properties of the left ventricle and leads to heart failure. In this study, we investigated the role of periostin, a matricellular protein, in the regulation of lysyl oxidase in cardiac fibroblasts in response to angiotensin II and TGFß1. Our results indicated that periostin silencing abolished the angiotensin II and TGFß1-mediated upregulation of lysyl oxidase. Furthermore, the attenuation of periostin expression resulted in a notable reduction in the activity of lysyl oxidase. Downstream of periostin, ERK1/2 MAPK signaling was found to be activated, which in turn transcriptionally upregulates the serum response factor to facilitate the enhanced expression of lysyl oxidase. The periostin-lysyl oxidase association was also positively correlated in an in vivo rat model of myocardial infarction. The expression of periostin and lysyl oxidase was upregulated in the collagen-rich fibrotic scar tissue of the left ventricle. Remarkably, echocardiography data showed a reduction in the left ventricular wall movement, ejection fraction, and fractional shortening, indicative of enhanced stiffening of the cardiac wall. These findings shed light on the mechanistic role of periostin in the collagen crosslinking initiated by activated cardiac fibroblasts. Our findings signify periostin as a possible therapeutic target to reduce excessive collagen crosslinking that contributes to the structural remodeling associated with heart failure.

Programmed ventricular stimulation in structural heart disease: Implications of patterns of ventricular arrhythmias induced to long-term outcomes.

INTRODUCTION: Currently available data gives some credence to utility of VT induction studies in patients with stable ischemic cardiomyopathy, there are some unresolved questions as to define sensitive threshold for low-risk and the prognostic relevance of ill sustained or non-specific tachycardia on induction study. We evaluated potential ability of VT inducibility to predict likelihood of SHD (Structural heart disease) patients for subsequent arrhythmic or adverse cardiac events. MATERIAL AND METHODS: All consecutive patients with syncope/documented arrhythmia who had VT induction done were included and patients with VT storm, ACS,uncontrolled HF were excluded. We studied in 4 groups-monomorphic VT, sustained polymorphicVT, ill sustainedVT/VF and no VT/VF induced. The primary-endpoints were - Sudden death, all-cause mortality and secondary-endpoints were - MACE (AICD shock, death,HF, recurrence of VT). We screened 411 patients and included 169 within inducible (n = 79) and non-inducible group (n = 90). RESULTS: There were a higher number of patients with coronary artery disease, LV dysfunction, patients on amiodarone in inducible group and no difference in usage of beta-blockers. Recurrence of VT, composite of MACE was significantly higher in inducible group (p < 0.05). Mortality was not different in 3 groups compared with no VT/VF group. We found that monomorphic VT group had significantly higher MACE as compared to others and also predicted recurrence of VT and AICD shock and showed a trend towards significance for prediction of mortality. Inducible patients on AICD had mortality similar to non-inducible group. CONCLUSION: Induction of monomorphicVT/polymorphicVT with ≤3extrastimuli is associated with a higher number of MACE events on follow up. Induction of monomorphicVT predicts recurrence of VT/ICD shock.