Thoracic aortic aneurysms in patients with heritable connective tissue disease

2021 ◽  
Vol 36 (3) ◽  
pp. 1083-1090
Author(s):  
Xuan Odofin ◽  
Nour Houbby ◽  
Arwa Hagana ◽  
Ibrahim Nasser ◽  
Amna Ahmed ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Aneurysms

scholarly journals Rare Causes of Arterial Hypertension and Thoracic Aortic Aneurysms—A Case-Based Review

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 446
Author(s):  
Svetlana Encica ◽  
Adrian Molnar ◽  
Simona Manole ◽  
Teodora Filan ◽  
Simona Oprița ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Aortic Aneurysm ◽  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Gene Mutations ◽  
Young Male ◽  
Renin Angiotensin System ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Aneurysms ◽  
Medial Degeneration

Thoracic aortic aneurysms may result in dissection with fatal consequences if undetected. A young male patient with no relevant familial history, after having been investigated for hypertension, was diagnosed with an ascending aortic aneurysm involving the aortic root and the proximal tubular segment, associated with a septal atrial defect. The patient underwent a Bentall surgery protocol without complications. Clinical examination revealed dorso–lumbar scoliosis and no other signs of underlying connective tissue disease. Microscopic examination revealed strikingly severe medial degeneration of the aorta, with areas of deep disorganization of the medial musculo–elastic structural units and mucoid material deposition. Genetic testing found a variant of unknown significance the PRKG1 gene encoding the protein kinase cGMP-dependent 1, which is important in blood pressure regulation. There may be genetic links between high blood pressure and thoracic aortic aneurysm determinants. Hypertension was found in FBN1 gene mutations encoding fibrillin and in PRKG1 mutations. Possible mechanisms involving the renin–angiotensin system, the role of oxidative stress, osteopontin, epigenetic modifications and other genes are reviewed. Close follow-up and strict hypertension control are required to reduce the risk of dissection. Hypertension, scoliosis and other extra-aortic signs suggesting a connective tissue disease are possible clues for diagnosis.

Elevated expression of connective tissue growth factor, osteopontin and increased collagen content in human ascending thoracic aortic aneurysms

Vascular ◽  
2013 ◽  
Vol 22 (1) ◽  
pp. 20-27 ◽  
Author(s):  
YH Meng ◽  
C Tian ◽  
L Liu ◽  
L Wang ◽  
Q Chang
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Aortic Aneurysms ◽  
Collagen Content ◽  
Control Group ◽  
Mrna Levels ◽  
Thoracic Aortic Aneurysms ◽  
Protein Levels

Little is known about the molecular mechanisms of ascending thoracic aortic aneurysms (ATAAs). Abnormal extracellular matrix changes and variations of vascular smooth muscle cells (VSMCs) have been implicated in abdominal aortic aneurysm formation. Our objective was to investigate the alterations of collagen, stimulators of collagen synthesis and synthetic VSMCs in patients with ATAA. Surgical samples from ATAA were taken from 20 patients, and 18 control aortas were obtained during coronary artery bypass surgery. All aortic wall specimens were fixed for histology and immunohistochemistry for collagen, connective tissue growth factor (CTGF) and osteopontin. Realtime polymerase chain reaction was used to determine their mRNA expression. Histology and semi-quantitative analysis demonstrated that protein levels of collagen, CTGF and osteopontin significantly increased by 1.9-, 1.4- and 2.2-fold, respectively ( P < 0.01 for all) in the ATAA group than in the control group. Similar results were shown in mRNA levels of type Iα1and IIIα1 collagen, CTGF and osteopontin. The protein levels of CTGF and osteopontin were positively correlated with aortic diameter ( r = 0.67, r = 0.73; P < 0.01 for both). In conclusion, overexpression of aortic CTGF and synthetic VSMCs marker (osteopontin), which is likely to be responsible for elevated aortic collagen content, may provide a potential mechanism for aneurysmal enlargement.

scholarly journals TGF-β Signaling-Related Genes and Thoracic Aortic Aneurysms and Dissections

2018 ◽  
Vol 19 (7) ◽  
pp. 2125 ◽  
Author(s):  
Norifumi Takeda ◽  
Hironori Hara ◽  
Takayuki Fujiwara ◽  
Tsubasa Kanaya ◽  
Sonoko Maemura ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Aortic Aneurysms ◽  
Loss Of Function ◽  
Angiotensin Ii Receptor ◽  
Thoracic Aortic Aneurysms ◽  
Structural Weakness ◽  
History Of

Transforming growth factor-β (TGF)-β signaling plays a crucial role in the development and maintenance of various organs, including the vasculature. Accordingly, the mutations in TGF-β signaling pathway-related genes cause heritable disorders of the connective tissue, such as Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and Shprintzen-Goldberg syndrome (SGS), and these syndromes may affect skeletal, ocular, pulmonary, and cardiovascular systems. Aortic root aneurysms are common problems that can result in aortic dissection or rupture, which is the leading cause of sudden death in the natural history of MFS and LDS, and recent improvements in surgical treatment have improved life expectancy. However, there is currently no genotype-specific medical treatment. Accumulating evidence suggest that not only structural weakness of connective tissue but also increased TGF-β signaling contributes to the complicated pathogenesis of aortic aneurysm formation, but a comprehensive understanding of governing molecular mechanisms remains lacking. Inhibition of angiotensin II receptor signaling and endothelial dysfunction have gained attention as a possible MFS treatment strategy, but interactions with TGF-β signaling remain elusive. Heterozygous loss-of-function mutations in TGF-β receptors 1 and 2 (TGFBR1 and TGFBR2) cause LDS, but TGF-β signaling is activated in the aorta (referred to as the TGF-β paradox) by mechanisms yet to be elucidated. In this review, we present and discuss the current understanding of molecular mechanisms responsible for aortopathies of MFS and related disorders.

Isolated aortic dilation without osteoarthritis: a case of SMAD3 mutation

2018 ◽  
Vol 28 (5) ◽  
pp. 765-767 ◽  
Author(s):  
Jose Arroyave ◽  
Juan Manuel Carretero ◽  
Domenico Gruosso
Keyword(s):  
Connective Tissue ◽  
Aortic Root ◽  
Early Onset ◽  
Autosomal Dominant ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Aortic Dilation ◽  
Arterial Tree ◽  
Thoracic Aortic Aneurysms ◽  
Almost All

AbstractAneurysm–osteoarthritis syndrome is a recently discovered inherited autosomal dominant connective tissue disease caused by SMAD3 mutations. Aneurysm–osteoarthritis syndrome is responsible for 2% of familial thoracic aortic aneurysms and dissections and is characterised by aneurysms, dissections, and tortuosity throughout the arterial tree in combination with osteoarthritis. Early-onset osteoarthritis is present in almost all patients. We present the case of a non-syndromic young boy with SMAD3 mutation isolated from the dilated aortic root and ascending aorta without osteoarthritis.

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