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25 záznamů v Medvik Filtry

Článek online

Novel LOX Variants in Five Families with Aortic/Arterial Aneurysm and Dissection with Variable Connective Tissue Findings

Van Gucht, Ilse
Autor Van Gucht, Ilse Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, 2650 Antwerp, Belgium
Krebsova, Alice
Autor Krebsova, Alice Department of Cardiology, IKEM, Praha 4, 14021 Prague, Czech Republic
Diness, Birgitte Rode
Autor Diness, Birgitte Rode Department of Clinical Genetics, Copenhagen University Hospital, 2100 Copenhagen, Denmark
Laga, Steven
Autor Laga, Steven Department of Cardiac Surgery, University of Antwerp and Antwerp University Hospital, 2650 Antwerp, Belgium
Adlam, Dave
Autor Adlam, Dave Acute and interventional Cardiology, University of Leicester, Leicester LE3 9QP, UK
Kempers, Marlies
Autor Kempers, Marlies Department of Human Genetics, Radboud University Medical Center, 6525 Nijmegen, The Netherlands
Samani, Nilesh J
Autor Samani, Nilesh J Acute and interventional Cardiology, University of Leicester, Leicester LE3 9QP, UK
Webb, Tom R
Autor Webb, Tom R Acute and interventional Cardiology, University of Leicester, Leicester LE3 9QP, UK
Baranowska, Ania A
Autor Baranowska, Ania A Acute and interventional Cardiology, University of Leicester, Leicester LE3 9QP, UK
Van Den Heuvel, Lotte
Autor Van Den Heuvel, Lotte Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, 2650 Antwerp, Belgium

International journal of molecular sciences. 2021 ; 22 (13) : . [pub] 20210701

Int J Mol Sci
ISSN 1422-0067
Medvik
Zdroj

Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in LOX, encoding the extracellular matrix crosslinking enzyme lysyl oxidase, have been reported to cause familial TAAD. Using a next-generation TAAD gene panel, we identified five additional probands carrying LOX variants, including two missense variants affecting highly conserved amino acids in the LOX catalytic domain and three truncating variants. Connective tissue manifestations are apparent in a substantial fraction of the variant carriers. Some LOX variant carriers presented with TAAD early in life, while others had normal aortic diameters at an advanced age. Finally, we identified the first patient with spontaneous coronary artery dissection carrying a LOX variant. In conclusion, our data demonstrate that loss-of-function LOX variants cause a spectrum of aortic and arterial aneurysmal disease, often combined with connective tissue findings.

MeSH
aneurysma hrudní aorty genetika patofyziologie MeSH
aorta metabolismus MeSH
arterie metabolismus MeSH
disekce aorty genetika patofyziologie MeSH
dospělí MeSH
genetická predispozice k nemoci genetika MeSH
lidé středního věku MeSH
lidé MeSH
lysyloxidasa genetika metabolismus MeSH
mutace genetika MeSH
nemoci pojiva genetika MeSH
pojivová tkáň metabolismus MeSH
rodokmen MeSH
Check Tag
dospělí MeSH
lidé středního věku MeSH
lidé MeSH
mužské pohlaví MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
kazuistiky MeSH

Článek online

Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues

eLife. 2018 ; 7 (-) : . [pub] 20181119

ISSN 2050-084X
Medvik
Zdroj

In vertebrates, head and trunk muscles develop from different mesodermal populations and are regulated by distinct genetic networks. Neck muscles at the head-trunk interface remain poorly defined due to their complex morphogenesis and dual mesodermal origins. Here, we use genetically modified mice to establish a 3D model that integrates regulatory genes, cell populations and morphogenetic events that define this transition zone. We show that the evolutionary conserved cucullaris-derived muscles originate from posterior cardiopharyngeal mesoderm, not lateral plate mesoderm, and we define new boundaries for neural crest and mesodermal contributions to neck connective tissue. Furthermore, lineage studies and functional analysis of Tbx1- and Pax3-null mice reveal a unique developmental program for somitic neck muscles that is distinct from that of somitic trunk muscles. Our findings unveil the embryological and developmental requirements underlying tetrapod neck myogenesis and provide a blueprint to investigate how muscle subsets are selectively affected in some human myopathies.

Článek

Expression of mRNAs related to connective tissue metabolism in rat hepatic stellate cells and myofibroblasts

Experimental and toxicologic pathology. 2007 ; 58 (4) : 263-273.

ISSN 0940-2993
Medvik
Zdroj

Hepatic stellate cells (HSC) and liver myofibroblasts (MFB) are two cell populations most likely responsible for the synthesis of most connective tissue components in fibrotic liver. They differ in their origin and location, and possibly in patterns of gene expression. Normal and carbon tetrachloride-cirrhotic livers from rats were used to isolate HSC. Liver was perfused with pronase and collagenase solutions, followed by centrifugation of the cell suspension on a density gradient. HSC were quiescent 2 days after plating on plastic but they became activated after another 5 days in culture. When the culture was passaged 5 times, its character changed profoundly as HSC were replaced by MFB. Microarray analysis was used to determine gene expression in quiescent HSC, activated HSC and MFB. The expression of 49 genes coding for connective tissue proteins, proteoglycans, metalloproteinases and their inhibitors, growth factors and cellular markers was determined. The pattern of gene expression changed during HSC activation and there were distinct differences between HSC and MFB. Little difference between normal cells and cells isolated from cirrhotic liver was found.