Elena Gallo MacFarlane

Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome

Emily E. Juzwiak, Caitlin J. Bowen, Rhiannon Edwards, Leda Restrepo et autres

Aortic dissection or rupture is a leading cause of mortality in vascular Ehlers-Danlos syndrome (VEDS), a disorder caused by mutations in the COL3A1 gene. Col3a1G938D/+ mice recapitulate features of VEDS, including high risk of aortic rupture. As in people with VEDS, aortic …

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Abstract Tu0014: Single cell RNA sequencing reveals adaptive and maladaptive transcriptional signature across aortic cell types in a mouse model of Autosomal Recessive Cutis Laxa type 1B

Wendy Espinoza Camejo, Emily E. Bramel, Leda Restrepo, Elena Gallo MacFarlane

Thoracic aorta aneurysms (TTA) are localized dilations that predispose the aorta to dissection or rupture. Autosomal Recessive Cutis Laxa type 1B (ARCL1B) is a connective tissue disorder caused by homozygous loss of function mutations in the EFEMP2/FBLN4 gene. This disorder is associated …

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Transforming growth factor-beta (TGF-β) in the pathogenesis of hereditary thoracic aneurysm disorders

Wendy A. Espinoza Camejo, Emily E. Bramel, Elena Gallo MacFarlane

The transforming growth factor-beta (TGF-β) signaling pathway regulates biological processes critical to embryonic development and tissue homeostasis, including cell proliferation, differentiation, adhesion and migration. Perturbations in TGF-β signaling are linked to a wide range of human diseases, including those affecting the cardiovascular …

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Abstract Tu0014: Single cell RNA sequencing reveals adaptive and maladaptive transcriptional signature across aortic cell types in a mouse model of Autosomal Recessive Cutis Laxa type 1B

Wendy Espinoza Camejo, Emily E. Bramel, Leda Restrepo, Elena Gallo MacFarlane

Thoracic aorta aneurysms (TTA) are localized dilations that predispose the aorta to dissection or rupture. Autosomal Recessive Cutis Laxa type 1B (ARCL1B) is a connective tissue disorder caused by homozygous loss of function mutations in the EFEMP2/FBLN4 gene. This disorder is associated …

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Chemokine (C-C Motif) Ligand 2 Expressing Adventitial Fibroblast Expansion During Loeys-Dietz Syndrome Aortic Aneurysm Formation

Alex R. Dalal, Albert J Pedroza, Jennifer L. Kim, Casey Gilles et autres

BACKGROUND: Loeys-Dietz syndrome (LDS), caused by mutations in the TGF-β (transforming growth factor-β) signaling cascade, leads to aggressive thoracic aneurysms. While vascular smooth muscle cell (SMC) phenotype modulation has been implicated in thoracic aneurysm formation, we sought to characterize the role of …

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Map2k6 is a potent genetic modifier of arterial rupture in vascular Ehlers-Danlos syndrome mice

Caitlin J. Bowen, Rebecca A. Sorber, Juan F. Calderón, Jefferson James Doyle et autres

Aortic dissection or rupture is a major cause of mortality in vascular Ehlers-Danlos syndrome (vEDS), a connective tissue disorder caused by heterozygous mutations in the collagen type III alpha 1 chain (COL3A1) gene. C57BL6/J (BL6) mice carrying the Col3a1G938D/+ mutation recapitulate the …

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Intrinsic GATA4 expression sensitizes the aortic root to dilation in a Loeys–Dietz syndrome mouse model

Emily E. Bramel, Wendy A. Espinoza Camejo, Tyler J. Creamer, Leda Restrepo et autres

Loeys–Dietz syndrome (LDS) is a connective tissue disorder caused by mutations that decrease transforming growth factor-β signaling. LDS-causing mutations increase the risk of aneurysm throughout the arterial tree, yet the aortic root is a site of heightened susceptibility. Here we investigate the …

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Intrinsic Gata4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model

Emily E. Bramel, Wendy Espinoza Camejo, Tyler J. Creamer, Leda Restrepo et autres

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Early clinical outcomes and molecular smooth muscle cell phenotyping using a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome

Albert J Pedroza, Paul P. Cheng, Alex R. Dalal, Kathrin Baeumler et autres

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Distinct Contribution of Global and Regional Angiotensin II Type 1a Receptor Inactivation to Amelioration of Aortopathy in Tgfbr1M318R/+ Mice

Emily E. Bramel, Rustam Bagirzadeh, Muzna Saqib, Tyler J. Creamer et autres

Angiotensin II (Ang II) type 1 receptor (AT1R) signaling controls both physiological and pathogenetic responses in the vasculature. In mouse models of Loeys-Dietz syndrome (LDS), a hereditary disorder characterized by aggressive aortic aneurysms, treatment with angiotensin receptor blockers (ARBs) prevents aortic root …

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Postnatal Smad3 Inactivation in Murine Smooth Muscle Cells Elicits a Temporally and Regionally Distinct Transcriptional Response

Emily E. Bramel, Tyler J. Creamer, Muzna Saqib, Wendy Nunez et autres

Heterozygous, loss of function mutations in positive regulators of the Transforming Growth Factor-β (TGF-β) pathway cause hereditary forms of thoracic aortic aneurysm. It is unclear whether and how the initial signaling deficiency triggers secondary signaling upregulation in the remaining functional branches of …

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Abstract 11068: Smad3-Deficiency in Murine Smooth Muscle Cells Causes Global Defects in Expression of Focal Adhesion Components, but Drives Subset-Specific Compensatory Mechanisms Promoting Matrix Degradation and Oxidative Stress

Emily E. Bramel, Tyler J. Creamer, Muzna Saqib, Wendy Nunez et autres

The pathogenesis of aortic aneurysms caused by mutations that impair TGF-β/Smad signaling without completely ablating it remains unclear. To investigate TGF-β’s role independently of its developmental functions, we used mouse models to inactivate Smad3 specifically in smooth muscle cells (SMCs) at 6 …

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