Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial

Groenink, Maarten; Hartog, Alexander W. den; Franken, Romy; Radonic, Teodora; Waard, Vivian de; Timmermans, Janneke; Scholte, Arthur J.; Berg, Maarten P. van den; Spijkerboer, Anje M.; Marquering, Henk A.; Zwinderman, Aeilko H.; Mulder, Barbara J.M.

doi:10.1093/eurheartj/eht334

Cited by 347 publications

(265 citation statements)

References 33 publications

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“…Cite this article as Cold Spring Harb Perspect Biol 2017;9:a022269 use of losartan was associated with a significant reduction in aortic root growth rate and also attenuated dilatation of the more distal ascending aorta in patients that had undergone aortic root replacement (Groenink et al 2013).…”

Section: Tgf-b Family Signaling In Connective Tissuesmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

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The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

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Section: Tgf-b Family Signaling In Connective Tissuesmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

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“…Основ-ной целью медикаментозного терапии при заболева-ниях аорты является снижение стресса сосудистой стенки пораженного сегмента аорты путем контроля артериального давления и сократительной функции сердца. Согласно литературным данным, пациентам с синдромом Марфана показано назначение бета-блокаторов, ингибиторов ангиотензин-превращаю-щего фермента и блокаторов рецепторов к ангио-тензину II типа [19][20]. Среди наших пациентов наличие АГ в послеоперационном периоде на яви-лось дополнительным фактором риска развития аневризм ТаАо (p=0,22).…”

Section: Discussionunclassified

The Condition of Distal Aorta After Proximal Reconstruction for Dissection in Marfan Syndrome

Чернявский¹,

Ляшенко²,

Сирота³

et al. 2016

Russ J Cardiol

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Marfan syndrome is a disease associated with high prevalence of aorta-related morbidity and mortality. Dissections and ruptures of thoracal aorta (ThAo) lead to decreased life duration in persons with Marfan syndrome with mediana at 30 year-old. Aim. To study the changes of distal aorta and clinical outcomes after surgical treatment for proximal aorta dissection in Marfan syndrome. Material and methods. In the SRICP, among patients operated for proximal aorta dissection, 14 were selected, who had histologically proven Marfan syndrome. They were followed-up. Results. In the long-term follow-up after the intervention on thoracoabdominal aorta (TAAo) was required in 2 patients. Reasons for transforming of the distal aorta were the age of the disease onset (p=0,04), acute stage of dissection (p=0,02). Changes in TAAo developed during first months after primary intervention, as in several years. Conclusion.Surgery for proximal dissections in Marfan syndrome patients is related to acceptable levels of morbidity and mortality in early and post-operation periods. Regular follow-up is required of such patients in post-operation period for on-time diagnostics and performing of secondary interventions.Russ J Cardiol 2016, 11 (139): 7-11 http://dx

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“…Nevertheless, there has been a constant debate surrounding the efficacy of ARBs compared to ACEIs, with both animal and human studies favoring the use of ARB (20). Losartan (ARB) has been found to limit the signaling effects of TGF-β, thereby reducing the damage caused by matrix degradation in the aortic wall (21). In 2008, shortly after Habashi et al (20) demonstrated that TGF-β was associated with aneurysm formation in mice, a cohort of 17 pediatric MFS patients were treated with losartan (22); follow up with serial echocardiograms demonstrated that the rate of increase in the aortic root diameter after ARB therapy was reduced amongst all patients compared to those untreated (3.54 vs. 0.46 mm/yr) (P<0.001) (22).…”

Section: Arbs and Angiotensin Converting Enzyme Inhibitors (Aceis)mentioning

confidence: 99%

Medical management of aortic disease in Marfan syndrome

Mahmood

Velásquez

Zafar

et al. 2017

Ann. Cardiothorac. Surg.

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Marfan syndrome (MFS) is a hereditary disorder with numerous pathophysiological effects, some specifically creating elastic dysfunction in cardiovascular organs. Aortic dilatation, dissection and rupture are major concerns in the management of MFS patients. Predilection to form aneurysms is an indication for prophylactic medical management of thoracic aortic aneurysm disease in these patients. The current guidelines describe β-blockers as the standard of care with angiotensin receptor blockers (ARBs) emerging as an equal, if not better alternative. We elaborate current evidence for and against different medical regimens used for the medical management of MFS patients.

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Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial

Abstract: In adult Marfan patients, losartan treatment reduces aortic root dilatation rate. After aortic root replacement, losartan treatment reduces dilatation rate of the aortic arch.

Cited by 347 publications

References 33 publications

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

The Condition of Distal Aorta After Proximal Reconstruction for Dissection in Marfan Syndrome

Medical management of aortic disease in Marfan syndrome

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