The biochemical response of the heart to hypertension and exercise

Wakatsuki, Toshiyuki; Schlessinger, Joseph; Elson, Elliot L.

doi:10.1016/j.tibs.2004.09.002

Cited by 91 publications

(79 citation statements)

References 69 publications

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“…Local cAMP levels and cardiac function Cardiac hypertrophy, an enlargement of heart-muscle cells, occurs in response to either exercise (physiological hypertrophy) or chronic hypertension (pathological hypertrophy) [48,49]. Physiological hypertrophy is beneficial because it enhances cardiac output to meet the increased metabolic demands of the body, whereas pathological hypertrophy is a major risk factor in the progression of heart failure [48,49].…”

Section: Akap Signaling Complexes: Makapsmentioning

confidence: 99%

“…Physiological hypertrophy is beneficial because it enhances cardiac output to meet the increased metabolic demands of the body, whereas pathological hypertrophy is a major risk factor in the progression of heart failure [48,49]. A model for cardiac hypertrophy is provided by the treatment of RNVs with hypertrophic agonists.…”

Section: Akap Signaling Complexes: Makapsmentioning

confidence: 99%

See 1 more Smart Citation

AKAP signaling complexes: getting to the heart of the matter

McConnachie

Langeberg

Scott

2006

Trends in Molecular Medicine

188

190

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Section: Akap Signaling Complexes: Makapsmentioning

confidence: 99%

Section: Akap Signaling Complexes: Makapsmentioning

confidence: 99%

AKAP signaling complexes: getting to the heart of the matter

McConnachie

Langeberg

Scott

2006

Trends in Molecular Medicine

188

190

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“…Dissecting the mechanical function and extracellular matrix (ECM) interactions of fibroblast cells is important for understanding wound healing (Tomasek et al 2002;Gabbiani 2003;Desmouliere et al 2005), pathologies such as fibrosis (Wakatsuki et al 2004) and thermal therapies (Xu et al 2008). An understanding of these functions and interactions may also be of importance for molecular-level treatments for diseases involving aberrant responses of cells to mechanical stress (e.g.…”

Section: Introductionmentioning

confidence: 99%

Whole cell mechanics of contractile fibroblasts: relations between effective cellular and extracellular matrix moduli

Marquez

Elson

Genin

2010

Phil. Trans. R. Soc. A.

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While much is known about the subcellular structures responsible for the mechanical functioning of a contractile fibroblast, debate exists about how these components combine to endow a cell with its form and mechanical function. We present an analysis of mechanical characterization experiments performed on bio-artificial tissue constructs, which we believe serve as a more realistic testing environment than two-dimensional cell culture. These model tissues capture many features of real tissues with the advantage that they can be engineered to model different physiological and pathological characteristics. We study here a model tissue consisting of reconstituted type I collagen and varying concentrations of activated contractile fibroblasts that is relevant to modelling different stages of wound healing. We applied this system to assess how cell and extracellular matrix (ECM) mechanics vary with cell concentration. Short-term and long-term moduli of the ECM were estimated through analytical and numerical analysis of two-phase elastic solids containing cell-shaped voids. The relative properties of cells were then deduced from the results of numerical analyses of two-phase elastic solids containing mechanically isotropic cells of varying modulus. With increasing cell concentration, the short-term and long-term tangent moduli of the reconstituted collagen ECM increased sharply from a baseline value, while those of the cells decreased monotonically.

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“…The ability of LC cells to respond to profibrotic triggers such as mechanical stress and transforming growth factor-β (TGF-β) resulting in enhanced ECM synthesis, implicates LC as an important pro-fibrotic tissue that could lead to loss of structural integrity resulting in collapse of LC and associated neuronal loss in gluacoma (Hernandez 2000 and. Endothelin-1 has been increasingly recognized for its role as a pro-fibrotic factor resulting in enhanced ECM synthesis and has been widely implicated in the pathology of various connective tissue disorders (Eng and Friedman 2000;Eddy 2000;Wakatsuki et al, 2004;Clozel and Salloukh 2005;Tsukada et al, 2006;Khan ZA 2006). We were therefore interested in studying the role ET-1 in regulation of collagens type I and VI in LC cells.…”

Section: Discussionmentioning

confidence: 99%

“…Intravitreal administration of ET-1 in various animal models results in loss of retinal ganglion cells by apoptosis, blockade of axonal transport, activation of optic nerve head astrocytes contributing to optic neuropathy similar to that observed in glaucoma (Stokely et al, 2002;Chauhan et al, 2004;Lau et al, 2006). ET-1 is also recognized as an important pro-fibrotic factor in initiating and maintaining fibrosis of various tissues, by enhancing collagen synthesis and deposition in several cell types including fibroblasts, cardiac myocytes, and smooth muscle cells (Eng and Friedman 2000;Eddy 2000;Wakatsuki et al, 2004;Clozel and Salloukh 2005;Tsukada et al, 2006;Khan ZA 2006). The role of ET-1 in the regulation of ECM collagens at the level of optic nerve head remains to be studied.…”

Section: Introductionmentioning

confidence: 99%

Endothelin-1 mediated regulation of extracellular matrix collagens in cells of human lamina cribrosa

Rao

Krishnamoorthy

Yorio

2008

Experimental Eye Research

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Endothelin-1(ET-1), a potent vaso-active peptide, mediates extracellular matrix regulation resulting in an increase in collagen deposition in various cell types and tissues and has been proposed to play a key role in glaucoma pathology. The role of ET-1 in the regulation of extracellular matrix collagens at the level of optic nerve head is not known. In this study we have examined the role of ET-1 in extracellular matrix collagen regulation in primary cultures of human lamina cribrosa cells. Our hypothesis is that ET-1 increases remodeling of the ECM of cells of the lamina cribrosa. Such actions could contribute to the development of optic neuropathy. QPCR analysis revealed that ET-1 mediated an increase in mRNA levels of collagen type I alpha 1 and collagen type VI alpha 1 chains at all doses of ET-1 with a significant increase at 1nM and 10nM concentration in LC cells. A dose dependent increase in collagen type I and type VI protein deposition and secretion was also observed by Western blot in response to ET-1 and was significant at 10nM and 100nM concentrations of ET-1. ET-1 increased the [ 3 H] proline uptake in LC cells suggesting that ET-1 contributed to an increase in total collagen synthesis in LC cells. ET-1 -mediated increase in collagen type I, type VI and total collagen synthesis was significantly blocked by the ET A receptor antagonist, BQ610, as well as with the ET B receptor antagonist, BQ788, suggesting the involvement of both receptor subtypes in ET-1 mediated collagen synthesis in LC cells. These results suggest that ET-1 regulates extra cellular matrix-collagen synthesis in LC cells and may contribute to ECM remodeling at the level of LC of POAG subjects who have elevated plasma and aqueous humor levels of endothelin-1.

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The biochemical response of the heart to hypertension and exercise

Cited by 91 publications

References 69 publications

AKAP signaling complexes: getting to the heart of the matter

AKAP signaling complexes: getting to the heart of the matter

Whole cell mechanics of contractile fibroblasts: relations between effective cellular and extracellular matrix moduli

Endothelin-1 mediated regulation of extracellular matrix collagens in cells of human lamina cribrosa

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