Background— For the majority of cases, the cause of spontaneous aortic dissection and rupture is unknown. An inherited risk is associated with Marfan syndrome, Ehlers-Danlos syndrome type IV, and loci mapped to diverse autosomal chromosomes. Analysis of pedigrees however has indicated that it may be also inherited as an X-linked trait. The biglycan gene, found on chromosome X in humans and mice, encodes a small leucine-rich proteoglycan involved in the integrity of the extracellular matrix. A vascular phenotype has never been described in mice deficient in the gene for small leucine-rich proteoglycans. In the breeding of BALB/cA mice homozygous for a null mutation of the biglycan gene, we observed that 50% of biglycan-deficient male mice died suddenly within the first 3 months of life. Methods and Results— Necropsies revealed a major hemorrhage in the thoracic or abdominal cavity, and histology showed aortic rupture that involved an intimal and medial tear as well as dissection between the media and adventitia. By transmission electron microscopy and biomechanical testing, the aortas of biglycan-deficient mice showed structural abnormalities of collagen fibrils and reduced tensile strength. Similar collagen fibril changes were observed in male as well as in female biglycan-deficient mice, which implies a role of additional determinants such as gender-related response to stress in the development of this vascular catastrophe only in male mice. Conclusions— The spontaneous death of biglycan-deficient male mice from aortic rupture implicates biglycan as essential for the structural and functional integrity of the aortic wall and suggests a potential role of biglycan gene defects in the pathogenesis of aortic dissection and rupture in humans.
Background The peptide hormone insulin-like factor 3 (INSL3) is a marker for Leydig cell function and the clinical use of serum INSL3 measurements has been suggested by several groups. Aim (1) To establish a reference range for liquid chromatography–tandem mass spectrometry (LC-MS/MS) of serum INSL3 in healthy boys and men; and (2) to compare the associations of serum INSL3 and testosterone (T) to pubertal stage, lifestyle factors, diurnal variation, body composition, and human chorionic gonadotropin (hCG) stimulation. Results In a reference range based on LC-MS/MS analysis of serum from 1073 boys and men, INSL3 increased from levels close to the detection limit (0.03 µg/L) in prepubertal boys to a maximum mean level of 1.3 µg/L (95% CI, 0.9-2.7) in young men (19-40 years of age) and decreased slightly in older men (0.1 µg/L per decade). Serum T, but not INSL3, was associated with body mass index or body fat percentage and with alcohol consumption. Smoking was positively associated with serum T, but negatively associated with INSL3. There were significant diurnal variations in both INSL3 and T in men (P < 0.001), but serum INSL3 varied substantially less, compared with serum T (± 11% vs ± 26%). Mean serum INSL3 increased after hCG stimulation, but less than T (+ 17% vs + 53%). In both healthy men and in patients suspected of testicular failure, baseline serum INSL3 was more closely associated to the hCG-induced increase in serum T than baseline T itself. Conclusion Measurement of serum INSL3 by LC-MS/MS has promise as a marker of testicular disorders.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.