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Mol Nutr Food Res. 2019 May 8:e1900022. doi: 10.1002/mnfr.201900022. [Epub ahead of print]

Maternal High-Sucrose Diet Accelerates Vascular Stiffness in Aged Offspring via Suppressing Cav 1.2 and Contractile Phenotype of Vascular Smooth Muscle Cells.

Author information

1
Institute for Fetology, First Hospital of Soochow University, Suzhou, 215006, China.
2
Department of Gastrointestinal Surgery, Tengzhou Central People's Hospital, Zaozhuang, 277500, China.
3
Obstetrics and Gynecology, Tengzhou Central People's Hospital, Zaozhuang, 277500, China.
4
Center for Prenatal Biology, Loma Linda University, Loma Linda, CA, 92350, USA.

Abstract

SCOPE:

The fetal programming in response to over-nutrition during pregnancy is involved in pathogenesis of cardiovascular diseases later in life. The authors' previous work reported that prenatal high-sucrose (HS) diet impaired functions of large-conductance Ca2+ -activated K+ channels (BK) in mesenteric arteries in the adolescent offspring rats. This study determines whether prenatal HS has a long-term impact on resistance vasculature in the aged offspring rats.

METHODS AND RESULTS:

Pregnant rats are fed with a high-sucrose diet until delivery. Aged offspring from prenatal HS exhibit elevated fasting insulin level, insulin resistance index, and diastolic pressure. Both pressure-induced myogenic responses and phenylephrine-stimulated contraction of mesenteric arteries in HS are weakened. Electrophysiological tests and western blot indicate that BK and L-type calcium channels (Cav 1.2) are impaired in HS group. On the other hand, expression of matrix metalloproteinase 2 of mesenteric arteries is reduced in HS group while expression of tissue inhibitors of metalloproteinase is increased, indicating that extra cellular matrix (ECM) is remodeled. Furthermore, expression of α-smooth muscle actin is decreased, and insulin/insulin receptor/phosphoinositide3-kinase (PI3K) signaling pathway is downregulated.

CONCLUSION:

The results suggest that prenatal HS induced stiffness of mesenteric arteries in aged offspring by inhibiting Cav 1.2 function and PI3K-associated contractile phenotype of VSMCs.

KEYWORDS:

L-type voltage-dependent calcium channel; aged offspring; prenatal high-sucrose; vascular smooth muscle cell phenotype; vascular stiffness

PMID:
31067604
DOI:
10.1002/mnfr.201900022

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