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Journal of the American Heart... Sep 2017
Topics: Animals; Aortic Aneurysm, Thoracic; Disease Models, Animal; Exercise; Marfan Syndrome
PubMed: 28947564
DOI: 10.1161/JAHA.117.007465 -
Journal of the American College of... Jun 2021
Topics: Cardiovascular System; Humans; Marfan Syndrome; Phenotype
PubMed: 34140104
DOI: 10.1016/j.jacc.2021.04.073 -
Circulation Research Feb 2019Current management of aortic aneurysms relies exclusively on prophylactic operative repair of larger aneurysms. Great potential exists for successful medical therapy... (Review)
Review
Current management of aortic aneurysms relies exclusively on prophylactic operative repair of larger aneurysms. Great potential exists for successful medical therapy that halts or reduces aneurysm progression and hence alleviates or postpones the need for surgical repair. Preclinical studies in the context of abdominal aortic aneurysm identified hundreds of candidate strategies for stabilization, and data from preoperative clinical intervention studies show that interventions in the pathways of the activated inflammatory and proteolytic cascades in enlarging abdominal aortic aneurysm are feasible. Similarly, the concept of pharmaceutical aorta stabilization in Marfan syndrome is supported by a wealth of promising studies in the murine models of Marfan syndrome-related aortapathy. Although some clinical studies report successful medical stabilization of growing aortic aneurysms and aortic root stabilization in Marfan syndrome, these claims are not consistently confirmed in larger and controlled studies. Consequently, no medical therapy can be recommended for the stabilization of aortic aneurysms. The discrepancy between preclinical successes and clinical trial failures implies shortcomings in the available models of aneurysm disease and perhaps incomplete understanding of the pathological processes involved in later stages of aortic aneurysm progression. Preclinical models more reflective of human pathophysiology, identification of biomarkers to predict severity of disease progression, and improved design of clinical trials may more rapidly advance the opportunities in this important field.
Topics: Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Antioxidants; Aortic Aneurysm, Abdominal; Humans; Marfan Syndrome; Protease Inhibitors
PubMed: 30763216
DOI: 10.1161/CIRCRESAHA.118.312439 -
Journal of the American Heart... Oct 2020
Topics: Androgens; Animals; Aortic Aneurysm, Thoracic; Fibrillin-1; Male; Marfan Syndrome; Mice; Transforming Growth Factor beta
PubMed: 33059494
DOI: 10.1161/JAHA.120.018814 -
Journal of the American College of... Mar 2020
Topics: Aortic Dissection; DNA Mutational Analysis; Fibrillin-1; Genetic Variation; Humans; Marfan Syndrome
PubMed: 32130919
DOI: 10.1016/j.jacc.2019.12.042 -
European Review For Medical and... Sep 2023Marfan syndrome (MFS) is a systemic connective tissue disease that commonly and most severely affects the ocular, skeletal, and cardiovascular systems. The aim of the... (Review)
Review
Marfan syndrome (MFS) is a systemic connective tissue disease that commonly and most severely affects the ocular, skeletal, and cardiovascular systems. The aim of the manuscript is to review the aortic involvement and complications in MFS, including aortal dissection, thoracic aortic aneurysm, abdominal aortic aneurysm, and acute aortic syndrome. Dissecting thoracic aortic aneurysm and progressing aortic root enlargement are the major causes of MFS morbidity and mortality. Guidelines on aortic disease endorsed by the American College of Cardiology, and the American Heart Association recommend the measurement of the external and internal aortic diameters perpendicular to the axis of blood flow when Computed Tomography, or Magnetic Resonance Imaging, or Cardiac Echography are performed. The pathophysiology, diagnosis, prevention, and medical and surgical treatments of MFS associated with aortic complications are reported in this narrative review. Development and strengthening of centers specialized in cardiovascular diseases and MFS, together with an improvement in the knowledge of its pathogenesis through genetics and proteomics investigations, can ameliorate the prognosis of this disease.
Topics: United States; Humans; Marfan Syndrome; Aorta; Aortic Dissection; Aortic Aneurysm, Abdominal; Acute Aortic Syndrome; Aortic Aneurysm, Thoracic
PubMed: 37750650
DOI: 10.26355/eurrev_202309_33582 -
The Journal of Thoracic and... Mar 2022
Topics: Fluoroquinolones; Humans; Marfan Syndrome
PubMed: 33189346
DOI: 10.1016/j.jtcvs.2020.10.057 -
Nigerian Journal of Clinical Practice May 2022
Topics: Humans; Marfan Syndrome; Treatment Outcome
PubMed: 35593622
DOI: 10.4103/njcp.njcp_131_22 -
Heart (British Cardiac Society) Oct 2023The eye is prone to various forms of afflictions, either as a manifestation of primary ocular disease or part of systemic disease, including the cardiovascular system. A... (Review)
Review
The eye is prone to various forms of afflictions, either as a manifestation of primary ocular disease or part of systemic disease, including the cardiovascular system. A thorough cardiovascular examination should include a brief ocular assessment. Hypertension and diabetes, for example, would present with retinopathy and dyslipidaemia would present with corneal arcus. Multisystem autoimmune diseases, such as Graves' disease, rheumatoid arthritis and sarcoidosis, would present with proptosis, episcleritis and scleritis, respectively. Myasthenia gravis, while primarily a neuromuscular disease, presents with fatigable ptosis and is associated with Takotsubo cardiomyopathy and giant cell myocarditis. Connective tissue diseases such as Marfan syndrome, which commonly presents with aortic root dilatation, would be associated with ectopia lentis and myopia. Wilson's disease, which is associated with arrhythmias and cardiomyopathies, would present usually with the characteristic Kayser-Fleischer rings. Rarer diseases, such as Fabry disease, would be accompanied by ocular signs such as cornea verticillata and such cardiac manifestations include cardiac hypertrophy as well as arrhythmias. This review examines the interplay between the eye and the cardiovascular system and emphasises the use of conventional and emerging tools to improve diagnosis, management and prognostication of patients.
Topics: Humans; Hepatolenticular Degeneration; Marfan Syndrome; Cardiovascular System; Heart; Copper
PubMed: 37507215
DOI: 10.1136/heartjnl-2022-322081 -
Nature Communications May 2021Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available...
Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets.
Topics: Animals; Aorta; Aortic Aneurysm, Thoracic; Biomarkers; Carbazoles; Cyclic GMP; Cyclic GMP-Dependent Protein Kinase Type I; Disease Models, Animal; Female; Fibrillin-1; Gene Knockdown Techniques; Humans; Male; Marfan Syndrome; Mice; Muscle, Smooth, Vascular; Mutation; Myocytes, Smooth Muscle; Nitric Oxide; Nitric Oxide Donors; Primary Cell Culture; Soluble Guanylyl Cyclase; Ultrasonography
PubMed: 33976159
DOI: 10.1038/s41467-021-22933-3