PMID- 35493479
OWN - NLM
STAT- MEDLINE
DCOM- 20220503
LR  - 20230402
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Elevated Expression of TLR2 in Aging Hearts Exacerbates Cardiac Inflammatory 
      Response and Adverse Remodeling Following Ischemia and Reperfusion Injury.
PG  - 891570
LID - 10.3389/fimmu.2022.891570 [doi]
LID - 891570
AB  - This study tested the hypothesis that Toll-like receptor 2 (TLR2) augments the 
      inflammatory responses and adverse remodeling in aging hearts to exacerbate 
      myocardial injury and cardiac dysfunction. METHODS: Old (20-22 months old) and 
      adult (4-6 months old) mice of C57BL/6 wild-type and TLR2 knockout (KO) were 
      subjected to coronary artery ligation (30 minutes) and reperfusion (3 or 14 
      days). Left ventricle function was assessed using a pressure-volume 
      microcatheter. Cardiac infarct size was determined by histology. Levels of 
      vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 
      (ICAM-1), matrix metalloproteinase 9 (MMP 9), and collagen I in non-ischemic 
      myocardium were assessed by immunoblotting. Monocyte chemoattractant protein-1 
      (MCP-1), keratinocyte chemoattractant (KC), and interleukin-6 (IL-6) levels in 
      ischemic and non-ischemic myocardium were measured by enzyme-linked immunosorbent 
      assay (ELISA). TLR2 expression in the myocardium of untreated wild type mice was 
      also measured by immunoblotting. RESULTS: Higher levels of MCP-1, KC, IL-6 were 
      induced in both ischemic and non-ischemic myocardium of old wild type mice at day 
      3 and 14 following ischemia/reperfusion (I/R) than those of adult wild type mice. 
      The hyper-inflammatory responses to I/R in aging hearts were associated with 
      elevated levels of myocardial TLR2. TLR2 KO markedly down-regulated the 
      expression of MCP-1, KC, IL-6, ICAM-1 and VCAM-1 in aging hearts at day 3 and 14 
      following I/R. The down-regulated inflammatory activity in aging TLR2 KO hearts 
      was associated with attenuated production of MMP 9 and collagen I at day 14 and 
      resulted in reduced infarct size and improved cardiac function. CONCLUSION: 
      Elevated expression of myocardial TLR2 contributes to the mechanism by which 
      aging exacerbates the inflammatory responses, adverse remodeling and cardiac 
      dysfunction following myocardial I/R in aging.
CI  - Copyright (c) 2022 Zhai, Ao, Yao, The, Fullerton and Meng.
FAU - Zhai, Yufeng
AU  - Zhai Y
AD  - Department of Surgery, University of Colorado Denver, Aurora, CO, United States.
FAU - Ao, Lihua
AU  - Ao L
AD  - Department of Surgery, University of Colorado Denver, Aurora, CO, United States.
FAU - Yao, Qingzhou
AU  - Yao Q
AD  - Department of Surgery, University of Colorado Denver, Aurora, CO, United States.
FAU - The, Erlinda
AU  - The E
AD  - Department of Surgery, University of Colorado Denver, Aurora, CO, United States.
FAU - Fullerton, David A
AU  - Fullerton DA
AD  - Department of Surgery, University of Colorado Denver, Aurora, CO, United States.
FAU - Meng, Xianzhong
AU  - Meng X
AD  - Department of Surgery, University of Colorado Denver, Aurora, CO, United States.
LA  - eng
GR  - R01 GM129641/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220414
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Interleukin-6)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Aging/physiology
MH  - Animals
MH  - Collagen
MH  - *Heart Diseases
MH  - Infarction
MH  - Intercellular Adhesion Molecule-1/genetics/metabolism
MH  - Interleukin-6
MH  - Ischemia
MH  - Matrix Metalloproteinase 9
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Reperfusion Injury
MH  - Toll-Like Receptor 2/metabolism
MH  - Vascular Cell Adhesion Molecule-1
PMC - PMC9046986
OTO - NOTNLM
OT  - TLR2
OT  - aging
OT  - inflammation
OT  - myocardial ischemia
OT  - remodeling
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/05/03 06:00
MHDA- 2022/05/04 06:00
PMCR- 2022/01/01
CRDT- 2022/05/02 06:20
PHST- 2022/03/07 00:00 [received]
PHST- 2022/03/22 00:00 [accepted]
PHST- 2022/05/02 06:20 [entrez]
PHST- 2022/05/03 06:00 [pubmed]
PHST- 2022/05/04 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.891570 [doi]
PST - epublish
SO  - Front Immunol. 2022 Apr 14;13:891570. doi: 10.3389/fimmu.2022.891570. eCollection 
      2022.