Loss of Caveolae, Vascular Dysfunction, and Pulmonary Defects in Caveolin-1 Gene-Disrupted Mice

Drab, Marek; Verkade, Paul; Elger, Marlies; Kasper, Michael; Löhn, Matthias; Lauterbach, Birgit; Menne, Jan; Lindschau, Carsten; Mende, Fanny; Luft, Friedrich C.; Schedl, Andreas; Haller, Hermann; Kurzchalia, Teymuras V.

doi:10.1126/science.1062688

Cited by 1,426 publications

(1,471 citation statements)

References 22 publications

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“…The function of caveolae remains controversial, but they are implicated in lipid regulation (Razani et al, 2002), endocytosis/transcytosis, and signal transduction (Okamoto et al, 1998;Drab et al, 2001;Matveev et al, 2001;Schlegel and Lisanti, 2001). Caveolae are particularly abundant in adipocytes and endothelial cells (Scherer et al, 1995).…”

Section: Resultsmentioning

confidence: 99%

Extensive vascularization of developing mouse ovaries revealed by caveolin‐1 expression

Bullejos

Bowles

Koopman

2002

Developmental Dynamics

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Expression screening for genes preferentially expressed in mouse fetal ovaries relative to testes identified Cav-1 as a candidate female-specific gene. Cav-1 encodes caveolin-1, a component of the cell membrane invaginations known as caveolae, which are involved in lipid regulation and signal transduction. In situ hybridization revealed high levels of Cav-1 mRNA in developing ovaries, compared with moderate or low levels in testes. Analysis of caveolin-1 protein distribution by immunofluorescence showed this difference to be due to the development of a dense and complex vascular network in the developing ovary. These observations point to a higher degree of differentiation and organization of the early stage mammalian ovary than previously suspected.

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Section: Resultsmentioning

confidence: 99%

Extensive vascularization of developing mouse ovaries revealed by caveolin‐1 expression

Bullejos

Bowles

Koopman

2002

Developmental Dynamics

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“…Associated with NO production, alterations in caveolin-1 abundance change vessels' ability to relax. Accordingly, increase in caveolin-1 expression has been associated with hypertension and its absence with vasodilatation due to eNOS hyperactivation (15,16). Moreover, the loss of caveolin-3 expression activates p42/44 MAPK cascade and induces cardiac hypertrophy (17).…”

Section: Discussionmentioning

confidence: 99%

Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice

Tı̂rziu¹,

Chorianopoulos²,

Moodie³

et al. 2007

J. Clin. Invest.

132

126

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Although studies have suggested a role for angiogenesis in determining heart size during conditions demanding enhanced cardiac performance, the role of EC mass in determining the normal organ size is poorly understood. To explore the relationship between cardiac vasculature and normal heart size, we generated a transgenic mouse with a regulatable expression of the secreted angiogenic growth factor PR39 in cardiomyocytes. A significant change in adult mouse EC mass was apparent by 3 weeks following PR39 induction. Heart weight; cardiomyocyte size; vascular density normalization; upregulation of hypertrophy markers including atrial natriuretic factor, β-MHC, and GATA4; and activation of the Akt and MAP kinase pathways were observed at 6 weeks post-induction. Treatment of PR39-induced mice with the eNOS inhibitor l-NAME in the last 3 weeks of a 6-week stimulation period resulted in a significant suppression of heart growth and a reduction in hypertrophic marker expression. Injection of PR39 or another angiogenic growth factor, VEGF-B, into murine hearts during myocardial infarction led to induction of myocardial hypertrophy and restoration of myocardial function. Thus stimulation of vascular growth in normal adult mouse hearts leads to an increase in cardiac mass.

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“…Caveolins-1 (α and β), −2 and −3, named for their association with caveolae (as well as lipid rafts), each contain a 33-aa hydrophobic domain that anchors the protein to the membrane (Anderson, 1998). Caveolin-1 in particular associates with invaginated caveolae, and its role in shaping the local membrane morphology is confirmed by the loss of flask-like caveolae in caveolin-1 null animals (Drab et al, 2001;Kranenburg et al, 2001). The protein structure of caveolins allows both amino and carboxyl termini to remain in the cell cytoplasm and interact with proteins that kink around the central hydrophobic domain.…”

Section: Membrane Structurementioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

402

303

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Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

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Loss of Caveolae, Vascular Dysfunction, and Pulmonary Defects in Caveolin-1 Gene-Disrupted Mice

Cited by 1,426 publications

References 22 publications

Extensive vascularization of developing mouse ovaries revealed by caveolin‐1 expression

Extensive vascularization of developing mouse ovaries revealed by caveolin‐1 expression

Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice

Molecular pathways mediating mechanical signaling in bone

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