Hypoxia promotes primitive glycosaminoglycan-rich extracellular matrix composition in developing heart valves

Dorothy Amofa, Alexia Hulin, Yuji Nakada, Hesham A. Sadek, Katherine E. Yutzey

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

During postnatal heart valve development, glycosaminoglycan (GAG)-rich valve primordia transform into stratified valve leaflets composed of GAGs, fibrillar collagen, and elastin layers accompanied by decreased cell proliferation as well as thinning and elongation. The neonatal period is characterized by the transition from a uterine environment to atmospheric O2, but the role of changing O2 levels in valve extracellular matrix (ECM) composition or morphogenesis is not well characterized. Here, we show that tissue hypoxia decreases in mouse aortic valves in the days after birth, concomitant with ECM remodeling and cell cycle arrest of valve interstitial cells. The effects of hypoxia on late embryonic valve ECM composition, Sox9 expression, and cell proliferation were examined in chicken embryo aortic valve organ cultures. Maintenance of late embryonic chicken aortic valve organ cultures in a hypoxic environment promotes GAG expression, Sox9 nuclear localization, and indicators of hyaluronan remodeling but does not affect fibrillar collagen content or cell proliferation. Chronic hypoxia also promotes GAG accumulation in murine adult heart valves in vivo. Together, these results support a role for hypoxia in maintaining a primitive GAG-rich matrix in developing heart valves before birth and also in the induction of hyaluronan remodeling in adults. NEW & NOTEWORTHY Tissue hypoxia decreases in mouse aortic valves after birth, and exposure to hypoxia promotes glycosaminoglycan accumulation in cultured chicken embryo valves and adult murine heart valves. Thus, hypoxia maintains a primitive extracellular matrix during heart valve development and promotes extracellular matrix remodeling in adult mice, as occurs in myxomatous disease.

Original languageEnglish (US)
Pages (from-to)H1143-H1154
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume313
Issue number6
DOIs
StatePublished - Dec 1 2017

Fingerprint

Heart Valves
Glycosaminoglycans
Extracellular Matrix
Aortic Valve
Fibrillar Collagens
Chickens
Organ Culture Techniques
Cell Proliferation
Parturition
Hyaluronic Acid
Embryonic Structures
Elastin
Cell Cycle Checkpoints
Hypoxia
Morphogenesis
Maintenance

Keywords

  • Extracellular matrix
  • Glycosaminoglycans
  • Heart valve development
  • Hypoxia
  • Sox9

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Hypoxia promotes primitive glycosaminoglycan-rich extracellular matrix composition in developing heart valves. / Amofa, Dorothy; Hulin, Alexia; Nakada, Yuji; Sadek, Hesham A.; Yutzey, Katherine E.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 313, No. 6, 01.12.2017, p. H1143-H1154.

Research output: Contribution to journalArticle

@article{2bfa8e75ac8241b3b493f48755ec70fa,
title = "Hypoxia promotes primitive glycosaminoglycan-rich extracellular matrix composition in developing heart valves",
abstract = "During postnatal heart valve development, glycosaminoglycan (GAG)-rich valve primordia transform into stratified valve leaflets composed of GAGs, fibrillar collagen, and elastin layers accompanied by decreased cell proliferation as well as thinning and elongation. The neonatal period is characterized by the transition from a uterine environment to atmospheric O2, but the role of changing O2 levels in valve extracellular matrix (ECM) composition or morphogenesis is not well characterized. Here, we show that tissue hypoxia decreases in mouse aortic valves in the days after birth, concomitant with ECM remodeling and cell cycle arrest of valve interstitial cells. The effects of hypoxia on late embryonic valve ECM composition, Sox9 expression, and cell proliferation were examined in chicken embryo aortic valve organ cultures. Maintenance of late embryonic chicken aortic valve organ cultures in a hypoxic environment promotes GAG expression, Sox9 nuclear localization, and indicators of hyaluronan remodeling but does not affect fibrillar collagen content or cell proliferation. Chronic hypoxia also promotes GAG accumulation in murine adult heart valves in vivo. Together, these results support a role for hypoxia in maintaining a primitive GAG-rich matrix in developing heart valves before birth and also in the induction of hyaluronan remodeling in adults. NEW & NOTEWORTHY Tissue hypoxia decreases in mouse aortic valves after birth, and exposure to hypoxia promotes glycosaminoglycan accumulation in cultured chicken embryo valves and adult murine heart valves. Thus, hypoxia maintains a primitive extracellular matrix during heart valve development and promotes extracellular matrix remodeling in adult mice, as occurs in myxomatous disease.",
keywords = "Extracellular matrix, Glycosaminoglycans, Heart valve development, Hypoxia, Sox9",
author = "Dorothy Amofa and Alexia Hulin and Yuji Nakada and Sadek, {Hesham A.} and Yutzey, {Katherine E.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1152/ajpheart.00209.2017",
language = "English (US)",
volume = "313",
pages = "H1143--H1154",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Hypoxia promotes primitive glycosaminoglycan-rich extracellular matrix composition in developing heart valves

AU - Amofa, Dorothy

AU - Hulin, Alexia

AU - Nakada, Yuji

AU - Sadek, Hesham A.

AU - Yutzey, Katherine E.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - During postnatal heart valve development, glycosaminoglycan (GAG)-rich valve primordia transform into stratified valve leaflets composed of GAGs, fibrillar collagen, and elastin layers accompanied by decreased cell proliferation as well as thinning and elongation. The neonatal period is characterized by the transition from a uterine environment to atmospheric O2, but the role of changing O2 levels in valve extracellular matrix (ECM) composition or morphogenesis is not well characterized. Here, we show that tissue hypoxia decreases in mouse aortic valves in the days after birth, concomitant with ECM remodeling and cell cycle arrest of valve interstitial cells. The effects of hypoxia on late embryonic valve ECM composition, Sox9 expression, and cell proliferation were examined in chicken embryo aortic valve organ cultures. Maintenance of late embryonic chicken aortic valve organ cultures in a hypoxic environment promotes GAG expression, Sox9 nuclear localization, and indicators of hyaluronan remodeling but does not affect fibrillar collagen content or cell proliferation. Chronic hypoxia also promotes GAG accumulation in murine adult heart valves in vivo. Together, these results support a role for hypoxia in maintaining a primitive GAG-rich matrix in developing heart valves before birth and also in the induction of hyaluronan remodeling in adults. NEW & NOTEWORTHY Tissue hypoxia decreases in mouse aortic valves after birth, and exposure to hypoxia promotes glycosaminoglycan accumulation in cultured chicken embryo valves and adult murine heart valves. Thus, hypoxia maintains a primitive extracellular matrix during heart valve development and promotes extracellular matrix remodeling in adult mice, as occurs in myxomatous disease.

AB - During postnatal heart valve development, glycosaminoglycan (GAG)-rich valve primordia transform into stratified valve leaflets composed of GAGs, fibrillar collagen, and elastin layers accompanied by decreased cell proliferation as well as thinning and elongation. The neonatal period is characterized by the transition from a uterine environment to atmospheric O2, but the role of changing O2 levels in valve extracellular matrix (ECM) composition or morphogenesis is not well characterized. Here, we show that tissue hypoxia decreases in mouse aortic valves in the days after birth, concomitant with ECM remodeling and cell cycle arrest of valve interstitial cells. The effects of hypoxia on late embryonic valve ECM composition, Sox9 expression, and cell proliferation were examined in chicken embryo aortic valve organ cultures. Maintenance of late embryonic chicken aortic valve organ cultures in a hypoxic environment promotes GAG expression, Sox9 nuclear localization, and indicators of hyaluronan remodeling but does not affect fibrillar collagen content or cell proliferation. Chronic hypoxia also promotes GAG accumulation in murine adult heart valves in vivo. Together, these results support a role for hypoxia in maintaining a primitive GAG-rich matrix in developing heart valves before birth and also in the induction of hyaluronan remodeling in adults. NEW & NOTEWORTHY Tissue hypoxia decreases in mouse aortic valves after birth, and exposure to hypoxia promotes glycosaminoglycan accumulation in cultured chicken embryo valves and adult murine heart valves. Thus, hypoxia maintains a primitive extracellular matrix during heart valve development and promotes extracellular matrix remodeling in adult mice, as occurs in myxomatous disease.

KW - Extracellular matrix

KW - Glycosaminoglycans

KW - Heart valve development

KW - Hypoxia

KW - Sox9

UR - http://www.scopus.com/inward/record.url?scp=85037047575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037047575&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00209.2017

DO - 10.1152/ajpheart.00209.2017

M3 - Article

C2 - 28842437

AN - SCOPUS:85037047575

VL - 313

SP - H1143-H1154

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 6

ER -