In this episode we explore ways in which the extracellular matrix can be manipulated, including the story of doxycycline, TGF-beta in Marfan syndrome and whether beta blockers can reduce vascular events in vascular EDS. ·        Intro 0:12 ·        Review of previous episode 0:28 ·        In this episode 2:26 ·        The pressure against the vessels 4:06 ·        The pressure against the wall 8:44 ·        Matrix metalloproteinases 10:16 ·        Tadpole study – collagen breakdown 10:35 ·        Tetracycline antibiotics 14:05 ·        Rat model – periodontal disease and hydroxyproline 14:24 ·        Chemically modified tetracyclines 20:14 ·        Mouse model – tetracycline use 22:00 ·        Tetracyclines and other autoimmune conditions 23:22 ·        Marfan syndrome 24:45 ·        Fibrillin and Marfan syndrome 28:48 ·        TGF-beta 29:36 ·        Mouse model – Marfan syndrome and fibrillin 31:14 ·        ARBs and TGF-beta 33:51 ·        TGF-beta and vascular EDS 37:25 ·        Back to the mouse model 38:38 ·        Protein kinase C 39:56 ·        Summary 40:26 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. References: Bowen CJ, et al. J Clin Invest. 2020;130:686-698. Brooke BS. Lancet. 2010;doi:10.1016/S0140-6736(10)61155-5 Dietz HC, et al. Am J Med Genet C Semin Med Genet. 2005;doi:10.1002/ajmg.c.30068. Dubacher N, et al. Cardiovasc Res. 2020;116:457-465. Golub LM, et al. SAGE. 1998;doi:10.1177/08959374980120010501. Gross J, et al. PNAS. 1962;doi:10.1073/pnas.48.6.1014 Habashi JP, et al. Science. 2006;312:117-121. Morissette R, et al. Circ Cardiovasc Genet. 2014;7:80-88. Mullen M, et al. Lancet. 2019;394:2263-2270. Neptune ER, et al. Nat Genet. 2003;33:407-411.