PMID- 36070095
OWN - NLM
STAT- MEDLINE
DCOM- 20230105
LR  - 20240102
IS  - 1615-2573 (Electronic)
IS  - 0910-8327 (Print)
IS  - 0910-8327 (Linking)
VI  - 38
IP  - 1
DP  - 2023 Jan
TI  - Cellular-scale sex differences in extracellular matrix remodeling by valvular 
      interstitial cells.
PG  - 122-130
LID - 10.1007/s00380-022-02164-2 [doi]
AB  - Males acquire calcific aortic valve disease (CAVD) twice as often as females, yet 
      stenotic valves from females display significantly higher levels of fibrosis 
      compared to males with similar extent of disease. Fibrosis occurs as an imbalance 
      between the production and degradation of the extracellular matrix (ECM), 
      specifically type I collagen. This work characterizes ECM production and 
      remodeling by male and female valvular interstitial cells (VICs) to better 
      understand the fibrocalcific divergence between sexes evident in CAVD. Male and 
      female VICs were assessed for gene and protein expression of myofibroblastic 
      markers, ECM components, matrix metalloproteinases (MMPs), and tissue inhibitors 
      of MMPs (TIMPs) via qRT-PCR and western blot. Overall metabolic activity was also 
      measured. Activity assays for collagenase and gelatinase were performed to 
      examine degradation behavior. Male VICs produced greater levels of 
      myofibroblastic markers while female VICs showed greater metabolic activity and 
      collagen production. In general, females displayed a greater level of MMP 
      expression and production than males, but no sex differences were observed in 
      TIMP production. Male VICs also displayed a greater level of collagenase and 
      gelatinase activity than female VICs. This work displays sex differences in ECM 
      remodeling by VICs that could be related to the sexual dimorphism in ECM 
      structure seen in clinical CAVD.
CI  - (c) 2022. Springer Japan KK, part of Springer Nature.
FAU - Simon, LaTonya R
AU  - Simon LR
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, 1111 
      Highland Ave, WIMR 8531, Madison, WI, 53705, USA.
FAU - Scott, Ashley J
AU  - Scott AJ
AD  - Cellular and Molecular Biology Training Program, University of Wisconsin-Madison, 
      Madison, WI, 53705, USA.
FAU - Figueroa Rios, Lysmarie
AU  - Figueroa Rios L
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, 1111 
      Highland Ave, WIMR 8531, Madison, WI, 53705, USA.
FAU - Zembles, Joshua
AU  - Zembles J
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, 1111 
      Highland Ave, WIMR 8531, Madison, WI, 53705, USA.
FAU - Masters, Kristyn S
AU  - Masters KS
AUID- ORCID: 0000-0001-6911-3116
AD  - Department of Biomedical Engineering, University of Wisconsin-Madison, 1111 
      Highland Ave, WIMR 8531, Madison, WI, 53705, USA. kmasters@wisc.edu.
AD  - Cellular and Molecular Biology Training Program, University of Wisconsin-Madison, 
      Madison, WI, 53705, USA. kmasters@wisc.edu.
AD  - Department of Medicine, School of Medicine and Public Health, University of 
      Wisconsin, Madison, WI, 53705, USA. kmasters@wisc.edu.
AD  - Department of Materials Science and Engineering, University of Wisconsin-Madison, 
      Madison, WI, 53705, USA. kmasters@wisc.edu.
LA  - eng
GR  - R21 EB019508/EB/NIBIB NIH HHS/United States
GR  - TL1 TR002375/TR/NCATS NIH HHS/United States
GR  - R01 HL141181/HL/NHLBI NIH HHS/United States
GR  - T32 GM140935/GM/NIGMS NIH HHS/United States
GR  - TL1TR002375/NH/NIH HHS/United States
GR  - TL1 TR000429/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20220907
PL  - Japan
TA  - Heart Vessels
JT  - Heart and vessels
JID - 8511258
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - Aortic Valve, Calcification of
SB  - IM
MH  - Male
MH  - Humans
MH  - Female
MH  - *Aortic Valve Stenosis
MH  - Aortic Valve/pathology
MH  - Sex Characteristics
MH  - *Calcinosis/pathology
MH  - Cells, Cultured
MH  - Extracellular Matrix
MH  - Gelatinases/metabolism
MH  - Fibrosis
MH  - Matrix Metalloproteinases/genetics
PMC - PMC10120251
MID - NIHMS1888873
OTO - NOTNLM
OT  - Extracellular matrix
OT  - Fibrosis
OT  - Remodeling
OT  - Sex differences
COIS- Conflict of interest The authors declare that they have no competing interests.
EDAT- 2022/09/08 06:00
MHDA- 2023/01/06 06:00
PMCR- 2024/01/01
CRDT- 2022/09/07 13:26
PHST- 2021/11/22 00:00 [received]
PHST- 2022/08/24 00:00 [accepted]
PHST- 2022/09/08 06:00 [pubmed]
PHST- 2023/01/06 06:00 [medline]
PHST- 2022/09/07 13:26 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 10.1007/s00380-022-02164-2 [pii]
AID - 10.1007/s00380-022-02164-2 [doi]
PST - ppublish
SO  - Heart Vessels. 2023 Jan;38(1):122-130. doi: 10.1007/s00380-022-02164-2. Epub 2022 
      Sep 7.