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TLR-Dependent Pathways and Akt/mTOR/P70S6K Pathways in Cardiac Remodeling After Myocardial Infarction

Chapter
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 5)

Abstract

Left ventricular remodeling is a progressive process which starts immediately after acute myocardial infarction (MI) and evolves in the chronic phase of heart failure. The molecular and cellular changes associated with ventricular remodeling affect both the cardiomyocytes and the interstitial space and manifest clinically as increased ventricular size, altered shape of the ventricle, and worsened cardiac function. Specific therapy to optimize healing and prevent adverse post-MI remodeling is currently lacking. Understanding of the specific events (time and space) that occur in response to MI and are involved in infarct healing is crucial to abrogate postinfarction ventricular remodeling and/or stimulate the healing process. Inflammation and extracellular matrix remodeling are two key components associated with LV remodeling after MI. Myocardial injury upon MI activates an inflammatory response that orchestrates the cardiac repair process through a complex cascade involving cytokines, other inflammatory mediators, and growth factors. In this regard, the innate immune system, such as that mediated by the Toll-like receptors (TLRs), has appeared during the past decade as a major contributor to the pathogenesis of MI by modulating cell survival and tissue injury. Cardiac remodeling also encompasses many changes in the myocardial interstitium leading to fibrosis and hypertrophy. The mammalian target of rapamycin (mTOR) signaling has shown to exert a broad spectrum of functions including cell cycle progression, hypertrophy, protein synthesis, autophagy, and angiogenesis, all of which largely contribute to the fibrotic reparative scar.

This chapter aims to provide an in-depth analysis of the contribution of both the innate immune system (via TLR activation) and the activation of Akt/mTOR/P70S6K in the cardiac remodeling phase post-MI.

Keywords

Myocardial infarction Cardiac remodeling Inflammation Innate immune system Toll-like receptor mTOR Hypertrophy Autophagy Fibrosis Matrix remodeling 

Abbreviations

HMGB

High-mobility group box

IL

Interleukin

IRF3

Interferon-regulatory factor-3

LV

Left ventricle

MI

Myocardial infarction

mTOR

Mammalian target of rapamycin

MyD88

Myeloid differentiation factor 88

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

PI3K

Phosphoinositide 3-kinase

TLR

Toll-like receptors

TNF

Tumor necrosis factor

TORC

mTOR complex

TRAF6

Tumor necrosis factor receptor-associated factor-6

TRAM

TRIF-related adaptor molecule

TRIF

TIR domain-containing adaptor protein inducing type 1 interferons

VEGF

Vascular endothelial growth factor

WT

Wild type

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant PauBarcelonaSpain
  2. 2.CIBEROBN-Pathophysiology of Obesity and NutritionBarcelonaSpain
  3. 3.UABBarcelonaSpain

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