Objective: Even though elastin and fibrillin-1 are the major structural components of elastic fibers, mutations in elastin and fibrillin-1 lead to narrowing of large arteries in supravalvular aortic stenosis and dilation of the ascending aorta in Marfan syndrome, respectively. A genetic approach was therefore used here to distinguish the differential contributions of elastin and fibrillin-1 to arterial development and compliance.
Methods And Results: Key parameters of cardiovascular function were compared among adult mice haploinsufficient for elastin (Eln(+/-)), fibrillin-1 (Fbn1(+/-)), or both proteins (dHet). Physiological and morphological comparisons correlate elastin haploinsufficiency with increased blood pressure and vessel length and tortuosity in dHet mice, and fibrillin-1 haploinsufficiency with increased aortic diameter in the same mutant animals. Mechanical tests confirm that elastin and fibrillin-1 impart elastic recoil and tensile strength to the aortic wall, respectively. Additional ex vivo analyses demonstrate additive and overlapping contributions of elastin and fibrillin-1 to the material properties of vascular tissues. Lastly, light and electron microscopy evidence implicates fibrillin-1 in the hypertension-promoted remodeling of the elastin-deficient aorta.
Conclusions: These results demonstrate that elastin and fibrillin-1 have both differential and complementary roles in arterial wall formation and function, and advance our knowledge of the structural determinants of vascular physiology and disease.
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http://dx.doi.org/10.1161/ATVBAHA.109.193227 | DOI Listing |
Cells
December 2024
Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Marfan syndrome is an inherited connective tissue disorder that affects the cardiovascular, musculoskeletal, and ocular systems. It is caused by pathogenic variants in the fibrillin-1 gene (). Fibrillin is a primary component of microfibrils, which are found throughout the extracellular matrix (ECM) and provide elasticity and resilience to connective tissue.
View Article and Find Full Text PDFCell Biochem Biophys
December 2024
Department of Biomaterials/Osaka Dental University, 8-1, Kuzuhahanazono-cho, Osaka, 573-1121, Japan.
Elastic fibers of the internal and external elastic laminae maintain blood vessel shapes. Impairment of smooth muscle cell function leads to vascular disease development. F-box and WD-40 domain-containing protein 2 (FBXW2) is associated with elastic fibers and osteocalcin expression for bone regeneration in the periosteum.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Biomedical Sciences Program, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA.
Marfan syndrome (MFS) is a systemic connective tissue disorder stemming from mutations in the gene encoding Fibrillin-1 (Fbn1), a key extracellular matrix glycoprotein. This condition manifests with various clinical features, the most critical of which is the formation of aortic root aneurysms. Reduced nitric oxide (NO) production due to diminished endothelial nitric oxide synthase (eNOS) activity has been linked to MFS aortic aneurysm pathology.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany.
Int J Cosmet Sci
November 2024
LVMH Recherche, Saint Jean de Braye, France.
Objective: Existing methods to evaluate skin care products suffer limitations. This is the case for ex vivo skin explants, a first-choice 3D model. While essential to analyse mid- to long-term biological effects, this classical model hinders assessing microrelief variations.
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