Angiotensin receptor blockade mediated amelioration of mucopolysaccharidosis type I cardiac and craniofacial pathology

Osborn, Mark J.; Webber, Beau R.; McElmurry, Ronald T.; Rudser, Kyle; DeFeo, Anthony P.; Muradian, Michael; Petryk, Anna; Hallgrímsson, Benedikt; Blazar, Bruce R.; Tolar, Jakub; Braunlin, Elizabeth

doi:10.1007/s10545-016-9988-z

Cited by 14 publications

(10 citation statements)

References 46 publications

(57 reference statements)

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“…Nevertheless, we found alteration neither in TGF-β levels nor in its canonical target (SMAD2/3) in heart samples. Per our data, a modest increase in TGF-β expression levels 41,50 with no activation of secondary messenger (p-SMAD2) was found in the aorta of MPS I mice. 50 As ERK, AKT, and TGF-β are related to collagen production, the reduced level of ERK and AKT activities and the unaltered levels of TGF-β, can explain, in part, the absence of collagen deposition on histological specimens.…”

Section: Discussionsupporting

confidence: 78%

“…On the other hand, given that RAS peptides and its receptors can be produced locally, heart RAS activation may play a more critical role in cardiovascular diseases, contrasting to systemic activation. Indeed, Osborn et al 41 showed a local up‐regulation of angiotensin II receptors type I and II and the activation of angiotensin II conversion enzyme I and II in the aortas of MPS I. Yet, in our study, we did not analyze the angiotensin peptides in the heart; we have analyzed the levels of AT1R, which was unaltered in heart samples.…”

Section: Discussionmentioning

confidence: 74%

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Cardiac pathology in mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling

Gonzalez

Leitão

Soares

et al. 2020

J of Inher Metab Disea

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Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, that codifies the alpha‐L‐iduronidase enzyme, which deficiency leads to storage of glycosaminoglycans, with multiple clinical manifestations. One of the leading causes of death in MPS I patients are cardiac complications such as cardiac valve thickening, conduction abnormalities, myocardial dysfunction, and cardiac hypertrophy. The mechanism leading to cardiac dysfunction in MPS I is not entirely understood. In a previous study, we have demonstrated that losartan and propranolol improved the cardiac function in MPS I mice. Thus, we aimed to investigate whether the pathways influenced by these drugs may modulate the cardiac remodeling process in MPS I mice. According to our previous observation, losartan and propranolol restore the heart function, without altering valve thickness. MPS I mice presented reduced activation of AKT and ERK1/2, increased activity of cathepsins, but no alteration in metalloproteinase activity was observed. Animals treated with losartan showed a reduction in cathepsin activity and restored ERK1/2 activation. While both losartan and propranolol improved heart function, no mechanistic evidence was found for propranolol so far. Our results suggest that losartan or propranolol could be used to ameliorate the cardiac disease in MPS I and could be considered as adjuvant treatment candidates for therapy optimization.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 74%

Cardiac pathology in mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling

Gonzalez

Leitão

Soares

et al. 2020

J of Inher Metab Disea

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“…In particular, they showed data indicating that treatments with an action similar to that of prednisolone may provide relief from at least some of the behavioral aspects of MPS IIIB disease. Osborn et al reported that angiotensin receptor blockade ameliorated MPS I cardiac and craniofacial pathology, suggesting a role for the renin angiotensin system (RAS) in MPS pathology (Osborn et al 2017).…”

Section: Discussionmentioning

confidence: 99%

P-Tau and Subunit c Mitochondrial ATP Synthase Accumulation in the Central Nervous System of a Woman with Hurler–Scheie Syndrome Treated with Enzyme Replacement Therapy for 12 Years

et al. 2018

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We report an autopsy case of a woman with mucopolysaccharidosis type I (MPS I) Hurler-Scheie syndrome who was treated with enzyme replacement therapy (ERT) for 12 years. This was the first case of MPS I treated with ERT in Japan. Pathological analysis showed no glycosaminoglycan accumulation in the liver and spleen as a result of long-term ERT, although severe aortic stenosis, diffuse intimal hyperplasia of the coronary artery, and fibrous hypertrophy of the endocardium were observed. Additionally, we detected subunit c mitochondrial ATP synthase (SCMAS) accumulation and mild tauopathy (hyperphosphorylated tau or p-tau, both 3-repeat and 4-repeat tau accumulation) in the same area of the cerebral limbic system and central gray matter of the mid brain and pons. Tauopathy is an important pathological finding in Alzheimer's disease and other neurodegenerative disorders; however, in MPS I, it is unclear whether tauopathy is a primary or secondary phenomenon. Thus, in this report, we describe pathological accumulation of p-tau and SCMAS in the context of MPS I and discuss the mechanisms and importance of these findings in the pathogenesis of MPS I.

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“…An interesting perspective comes from mouse model studies, i.e. the potential use of losartan, an angiotensin-1 receptor antagonist, to treat aortopathy in patients with MPS (as in patients with aortopathy related to Marfan syndrome) [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Early diagnosis and management of cardiac manifestations in mucopolysaccharidoses: a practical guide for paediatric and adult cardiologists

Boffi¹,

Russo²,

Limongelli

2018

Ital J Pediatr

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Mucopolysaccharidoses (MPS) are a group of hereditary disorders caused by lysosomal storage of glycosaminoglycans (GAGs) and characterized by a wide variability of phenotypes from severe fetal-neonatal forms to attenuated diseases diagnosed in adult individuals. The clinical picture generally worsens with age due to progressive storage involving mucosal tissue, upper airways and lungs, bones and joints, central and peripheral nervous system, heart, liver, eye, and ear. Cardiac storage of GAGs involves valves, heart muscle, and vessels (particularly the coronary arteries), and can be specific in relation to different MPS types and enzyme defects. MPS I, II, and VI are those with the most severe cardiac involvement. The cardiologist is a key figure in MPS, and their role is expanding from cardiac-specific management to early diagnosis when the mild disease phenotypes have not yet been recognized by other specialists. Familial and personal history, electrocardiography, imaging, and laboratory findings represent important steps in the clinical investigation of these patients. New treatments have led to an increased need for cardiologists to be on the lookout for MPS patients since they can significantly improve the lives of people with MPS if they suspect the diagnosis and refer them for enzyme replacement therapy or bone marrow transplantation.

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Angiotensin receptor blockade mediated amelioration of mucopolysaccharidosis type I cardiac and craniofacial pathology

Cited by 14 publications

References 46 publications

Cardiac pathology in mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling

Cardiac pathology in mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling

P-Tau and Subunit c Mitochondrial ATP Synthase Accumulation in the Central Nervous System of a Woman with Hurler–Scheie Syndrome Treated with Enzyme Replacement Therapy for 12 Years

Early diagnosis and management of cardiac manifestations in mucopolysaccharidoses: a practical guide for paediatric and adult cardiologists

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