Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology

Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology

Conrad P. Hodgkinson, Akshay Bareja, José A. Gomez, Victor J. Dzau

Paracrine factors are pleiotropic. For illustration, we show the cellular effects of 2 selective paracrine factors on the cardiomyocyte. Left, Hypoxic-induced Akt regulated stem cell factor (HASF) and secreted frizzled related protein 2 (Sfrp2) inhibit cardiomyocyte apoptosis through divergent pathways. HASF, after binding to a growth factor receptor, inhibits cytochrome release from mitochondria via protein kinase C-ε (PKCε). In contrast, Sfrp2 inhibits Wnt activation of frizzled receptors. This induces β-catenin degradation via the anaphase promoting complex (APC) complex. Right, Abi3bp and Sfrp2 promote cardiac progenitor cell differentiation and inhibiting proliferation. Abi3bp activates integrin-β1. Src and extracellular signal regulated kinase (ERK) activation work together to inhibit proliferation. PKCζ and Akt activation switch on cardiac genes. Sfrp2 sequesters Wnt, preventing the activation of frizzled receptors. This promotes c-Jun N-terminal kinase (JNK) activation and cardiac gene expression. Inhibition of β-catenin blocks the proliferation pathway in these cells. ECM indicates extracellular matrix; FRZ, frizzled; and TF, transcription factor. [Powerpoint File]

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