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Review
. 2003 Oct;14(5):391-407.
doi: 10.1016/s1359-6101(03)00044-3.

Transforming growth factor beta in cardiovascular development and function

Mohamad Azhar  1 , Jo El J Schultz, Ingrid Grupp, Gerald W Dorn 2nd, Pierre Meneton, Daniel G M Molin, Adriana C Gittenberger-de Groot, Thomas Doetschman
Affiliations
Review

Transforming growth factor beta in cardiovascular development and function

Mohamad Azhar et al. Cytokine Growth Factor Rev. 2003 Oct.

Abstract

Transforming growth factor betas (TGFbetas) are pleiotropic cytokines involved in many biological processes. Genetic engineering and tissue explanation studies have revealed specific non-overlapping roles for TGFbeta ligands and their signaling molecules in development and in normal function of the cardiovascular system in the adult. In the embryo, TGFbetas appear to be involved in epithelial-mesenchymal transformations (EMT) during endocardial cushion formation, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. In the adult, TGFbetas are involved in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system. The evidence for TGFbeta activities during cardiovascular development and physiologic function will be given and areas which need further investigation will be discussed.

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Figures

Fig. 1
Fig. 1
TGFβ signaling can occur through multiple pathways. Many of these pathways are SMAD dependent, but there is evidence that pathways involving MAPK and FKBP12/Ca2+/calcineurin may be SMAD independent. The integrin pathway in platelets is independent of transcription.
Fig. 2
Fig. 2
Expression of Tg fb2 and Tg fb3 in wildtype embryonic hearts. In situ hybridization (B, C, E, F, H, I, K–O) and cardiac α-actin antibody HHF35 (A, D, G) or α-smooth muscle actin antibody 1A4 (J). A: primitive atrium; Ao: ascending aorta; AoS: aortic sac; AoV: aortic valve; AVC: AV cushion; CM: condensed mesenchyme; DAo: dorsal aorta; LA: left atrium; OT: outflow tract; PT: pulmonary trunk; PV: pulmonary valve; RV: right ventricle; V: primitive ventricle. Bars: A–L, 100 nm; M–O, 200 nm.
Fig. 3
Fig. 3
Endocardial epithelial–mesenchymal transformation (A) to form endocardial cushions (E9.5) and myocardialization (B) to form muscularized OT/AV septum (E12.5–16.5). OTC: outflow tract cushion; AVC: atrio-ventricular cushion; IC: inner curvature; M: myocardium; IVS: interventricular septum, RV: right ventricle; LV: left ventricle.
Fig. 4
Fig. 4
Histochemical analysis of E15.5 Tg fb2 and Tg fb3 KO hearts at the ventricular wall (G–I) and aortic arch artery (A–F). AoA: aortic arch; DAo: dorsal aorta; LV: left ventricle, Oe: oesophagus; RV: right ventricle. Bars: A–F, 100 nm; G–I, 200 nm.
Fig. 5
Fig. 5
Morphometric analysis of ventricular myocardial and lumen volumes of E14.5 & E15.5 Tg fb2+/+ and Tg fb2−/− embryos. Paired t-test comparison between Tg fb2+/+ and Tg fb2−/− embryos at E14.5 and E15.5.
Fig. 6
Fig. 6
Diastolic and β-adrenergic deficiency in Tg fb1−/− hearts. Isolated, work-performing hearts from adult Tg fb1−/− Scid mice (A). β-Adrenergic-stimulated contractility (+dP/dt) and relaxation (−dP/dt) rates in LFA-1 antibody-treated adult Tg fb1−/− mice. Immunodeficiency (Scid) or immunosuppression (LFA-1 antibody treatment) is required to circumvent weaning age lethality (see Section 3.2 for explanation). IVP: interventricular pressure.
Fig. 7
Fig. 7
Thromboxane induces mitotic growth of Tg fb1−/− VSMC. Quiescent VSMC derived from Tg fb1+/+ and Tg fb1−/− mice were stimulated with vehicle or 1 μM U44619. [3H]thymidine (A) and [3H]leucine incorporation (B) after 24 and 48 h exposure, respectively. n = 7, (*) P < 0.05 vs. Tg fb1+/+ mice).
Fig. 8
Fig. 8
Determination of renal renin mRNA and protein levels in the kidneys of hydrated or dehydrated Tg fb2+/+ and Tg fb2+/− mice. The relative intensity of the renin signal was estimated as the sum of intensities for each glomerulus, divided by the number of glomeruli observed [140].
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References

    1. Massague J, Chen YG. Controlling TGF-beta signaling. Genes Dev. 2000;14:627–44. - PubMed
    1. Sporn MB, Roberts AB. Transforming growth factor-beta: recent progress and new challenges. J Cell Biol. 1992;119:1017–21. review. - PMC - PubMed
    1. Heine U, Munoz EF, Flanders KC, Ellingsworth LR, Lam HY, Thompson NL, et al. Role of transforming growth factor-beta in the development of the mouse embryo. J Cell Biol. 1987;105:2861–76. - PMC - PubMed
    1. Pelton RW, Saxena B, Jones M, Moses HL, Gold LI. Immunohistochemical localization of TGF beta 1–3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J Cell Biol. 1991;115:1091–105. - PMC - PubMed
    1. Sanford LP, Ormsby I, Gittenberger-de GA, Sariola H, Friedman R, Boivin GP, et al. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development. 1997;124:2659–70. - PMC - PubMed

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