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  Indian J Med Microbiol
 

Figure 6: Diagrammatic representation of main intracellular signaling pathways regulating cardiac hypertrophy. Elevated calcium ion levels downstream of GPCRs, either through activation of voltage-gated calcium channels or from intracellular stores, is sensed by calmodulin, which activates calcineurin. Calcineurin in turn dephosphorylates NFAT transcription factor, leading to its nuclear translocation, where it activates gene transcription. ROS can contribute to hypertrophy by direct interaction with cellular proteins and subsequent changes in cellular contraction and/or induction of apoptosis, or by activation of NFkB mediated gene transcription. Inflammatory stimuli can exacerbate the disease condition by inducing interstitial inflammatory cell infiltration and fibrosis. Stress signals can trigger the activation MAP kinase cascades, which activate a number of downstream targets such as JNK, finally leading to transcriptional activation. Growth hormones induced by physiological cues, such as exercise or pregnancy, bind to and activate downstream signaling of RTKs, which, on the other hand, leads to adaptive hypertrophic growth. GPCR = G-protein-coupled receptor, RTK = Receptor tyrosine kinase, MAPKKs = Mitogenactivated protein kinase kinases, ROS = Reactive oxygen species, RyR = Ryanodine receptor, PI3K = Phosphoinositide-3 kinase, JNK = c-Jun N-terminal kinase, NFkB = Nuclear factor kappa B, PKC = Protein kinase C, Cam = Calmodulin, CnA = Calcineurin A, CnB = Calcineurin B, NFAT = Nuclear factor of activated T-cell, Akt = Protein kinase B (PKB), mTOR = Mammalian target of rapamycin, LPS = Lipopolysaccharide. Reproduced with permission

Figure 6: Diagrammatic representation of main intracellular signaling pathways regulating cardiac hypertrophy. Elevated calcium ion levels downstream of GPCRs, either through activation of voltage-gated calcium channels or from intracellular stores, is sensed by calmodulin, which activates calcineurin. Calcineurin in turn dephosphorylates NFAT transcription factor, leading to its nuclear translocation, where it activates gene transcription. ROS can contribute to hypertrophy by direct interaction with cellular proteins and subsequent changes in cellular contraction and/or induction of apoptosis, or by activation of NFkB mediated gene transcription. Inflammatory stimuli can exacerbate the disease condition by inducing interstitial inflammatory cell infiltration and fibrosis. Stress signals can trigger the activation MAP kinase cascades, which activate a number of downstream targets such as JNK, finally leading to transcriptional activation. Growth hormones induced by physiological cues, such as exercise or pregnancy, bind to and activate downstream signaling of RTKs, which, on the other hand, leads to adaptive hypertrophic growth. GPCR = G-protein-coupled receptor, RTK = Receptor tyrosine kinase, MAPKKs = Mitogenactivated protein kinase kinases, ROS = Reactive oxygen species, RyR = Ryanodine receptor, PI3K = Phosphoinositide-3 kinase, JNK = c-Jun N-terminal kinase, NFkB = Nuclear factor kappa B, PKC = Protein kinase C, Cam = Calmodulin, CnA = Calcineurin A, CnB = Calcineurin B, NFAT = Nuclear factor of activated T-cell, Akt = Protein kinase B (PKB), mTOR = Mammalian target of rapamycin, LPS = Lipopolysaccharide. Reproduced with permission