HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes

BACKGROUND: We previously demonstrated the small heat shock protein, HSPB1, to prevent tachycardia remodeling in in vitro and in vivo models for Atrial Fibrillation (AF). To gain insight into its mechanism of action, we examined the protective effect of all 10 members of the HSPB family on tachycardia remodeling. Furthermore, modulating effects of HSPB on RhoA GTPase activity and F-actin stress fiber formation were examined, as this pathway was found of prime importance in tachycardia remodeling events and the initiation of AF. METHODS AND RESULTS: Tachypacing (4 Hz) of HL-1 atrial myocytes significantly and progressively reduced the amplitude of Ca²⁺ transients (CaT). In addition to HSPB1, also overexpression of HSPB6, HSPB7 and HSPB8 protected against tachypacing-induced CaT reduction. The protective effect was independent of HSPB1. Moreover, tachypacing induced RhoA GTPase activity and caused F-actin stress fiber formation. The ROCK inhibitor Y27632 significantly prevented tachypacing-induced F-actin formation and CaT reductions, showing that RhoA activation is required for remodeling. Although all protective HSPB members prevented the formation of F-actin stress fibers, their mode of action differs. Whilst HSPB1, HSPB6 and HSPB7 acted via direct prevention of F-actin formation, HSPB8-protection was mediated via inhibition of RhoA GTPase activity. CONCLUSION: Overexpression of HSPB1, as well as HSPB6, HSPB7 and HSPB8 independently protect against tachycardia remodeling by attenuation of the RhoA GTPase pathway at different levels. The cardioprotective role for multiple HSPB members indicate a possible therapeutic benefit of compounds able to boost the expression of single or multiple members of the HSPB family

The Assessment of a Predictive Risk and a Decrease Postoperative Complication Following Body-Contouring Surgery After Massive Weight Loss

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Les cicatrices chéloïdes (deuxième partie) : arsenal et stratégie thérapeutique

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Les cicatrices chéloïdes (première partie) : une pathologie de la cicatrisation cutanée

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Hawkins' type-II talar fracture with subtalar dislocation: A very unusual combination

We report the unusual case of a 16-year-old young man who sustained a rare association of a Hawkins' type-II talar neck fracture with a complete medial subtalar dislocation (Hawkins type-IIB) that occurred as an isolated injury after indirect trauma during a soccer game. Following closed reduction of the subtalar dislocation, standard radiographs and computed tomography (CT) demonstrated a comminuted fracture of the talus involving the base of the talar neck. Open reduction was performed and the fracture was stabilized by ORIF. At 1-year follow-up, functional and radiographic outcomes were graded as excellent, with no radiographic evidence of talar osteonecrosis

Mineralocorticoid receptor antagonism prevents the electrical remodeling that precedes cellular hypertrophy after myocardial infarction.

International audienceBackground— Cardiac hypertrophy underlies arrhythmias and sudden death, for which mineralocorticoid receptor (MR) activity has recently been implicated. We sought to establish the sequence of ionic events that link the initiating insult and MR to hypertrophy development. Methods and Results— Using whole-cell, patch-clamp and quantitative reverse transcription–polymerase chain reaction techniques on right ventricular myocytes of a myocardial infarction (MI) rat model, we examined the cellular response over time. One week after MI, no sign of cellular hypertrophy was found, but action potential duration (APD) was lengthened. Both an increase in Ca 2+ current ( I Ca ) and a decrease in K + transient outward current ( I to ) underlay this effect. Consistently, the relative expression of mRNA coding for the Ca 2+ channel α1C subunit (Ca v 1.2) increased, and that of the K + channel K v 4.2 subunit decreased. Three weeks after MI, AP prolongation endured, whereas cellular hypertrophy developed. I Ca density, Ca v 1.2, and K v 4.2 mRNA levels regained control levels, but I to density remained reduced. Long-term treatment with RU28318, an MR antagonist, prevented this electrical remodeling. In a different etiologic model of abdominal aortic constriction, we confirmed that APD prolongation and modifications of ionic currents precede cellular hypertrophy. Conclusions— Electrical remodeling, which is triggered at least in part by MR activation, is an initial, early cellular response to hypertrophic insults