Specific Local Cardiovascular Changes of N-epsilon-(Carboxymethyl)lysine, Vascular Endothelial Growth Factor, and Smad2 in the Developing Embryos Coincide With Maternal Diabetes-Induced Congenital Heart Defects

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Roest, Pauline A.M.Department of Embryology and Anatomy, Leiden University (author)

Specific Local Cardiovascular Changes of N-epsilon-(Carboxymethyl)lysine, Vascular Endothelial Growth Factor, and Smad2 in the Developing Embryos Coincide With Maternal Diabetes-Induced Congenital Heart Defects

Article/chapterEnglish2009

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2009-02-02
American Diabetes Association,2009
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LIBRIS-ID:oai:DiVA.org:uu-142728
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-142728URI
https://doi.org/10.2337/db07-1016DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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OBJECTIVE: Embryos exposed to a diabetic environment in utero have an increased risk to develop congenital heart malformations. The mechanism behind the teratogenicity of diabetes still remains enigmatic. Detrimental effects of glycation products in diabetic patients have been well documented. We therefore studied a possible link between glycation products and the development of congenital cardiovascular malformations. Furthermore, we investigated other possible mechanisms involved in this pathogenesis: alterations in the levels of vascular endothelial growth factor (VEGF) or phosphorylated Smad2 (the latter can be induced by both glycation products and VEGF). RESEARCH DESIGN AND METHODS: We examined the temporal spatial patterning of the glycation products Nepsilon(carboxymethyl)lysine (CML) and methylglyoxal (MG) adducts, VEGF expression, and phosphorylated Smad2 during cardiovascular development in embryos from normal and diabetic rats. RESULTS: Maternal diabetes increased the CML accumulation in the areas susceptible to diabetes-induced congenital heart disease, including the outflow tract of the heart and the aortic arch. No MG adducts could be detected, suggesting that CML is more likely to be indicative for increased oxidative stress than for glycation. An increase of CML in the outflow tract of the heart was accompanied by an increase in phosphorylated Smad2, unrelated to VEGF. VEGF showed a time-specific decrease in the outflow tract of embryos from diabetic dams. CONCLUSIONS: From our results, we can conclude that maternal diabetes results in transient and localized alterations in CML, VEGF expression, and Smad2 phosphorylation overlapping with those regions of the developing heart that are most sensitive to diabetes-induced congenital heart disease.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
Diabetology
Diabetologi
Toxicology
Toxikologi

Added entries (persons, corporate bodies, meetings, titles ...)

Molin, Daniël G. M.Department of Embryology and Anatomy, Leiden University (author)
Schalkwijk, Casper G.Department of Embryology and Anatomy, Leiden University (author)
van Iperen, LiesbethDepartment of Embryology and Anatomy, Leiden University (author)
Wentzel, Parri,1948-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)parrwent (author)
Eriksson, Ulf J.,1948-Uppsala universitet,Institutionen för medicinsk cellbiologi (author)
Gittenberger-de Groot, Adriana C.Department of Embryology and Anatomy, Leiden University (author)
Department of Embryology and Anatomy, Leiden UniversityInstitutionen för medicinsk cellbiologi (creator_code:org_t)

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In:Diabetes: American Diabetes Association58:5, s. 1222-12280012-17971939-327X

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