PMID- 38094127
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240131
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 10
DP  - 2023
TI  - Aging exacerbates cardiac dysfunction and mortality in sepsis through enhancing 
      TLR2 activity.
PG  - 1293866
LID - 10.3389/fcvm.2023.1293866 [doi]
LID - 1293866
AB  - INTRODUCTION: Sepsis is prevalent in the elderly population with increased 
      incidence and mortality. Currently, the mechanism by which aging increases the 
      susceptibility to sepsis and worsens outcome is unclear. We tested the hypothesis 
      that aging exacerbates cardiac dysfunction in sepsis through a Toll-like receptor 
      2 (TLR2)-dependent mechanism. METHODS: Male young adult (4-6 months) and old 
      (18-20 months) wild type (WT) and TLR2 knockout (KO) mice were subject to 
      moderate sepsis by cecal ligation and puncture. Additional groups of young adult 
      and old WT mice were treated with TLR2 agonist Pam3CSK4. Left ventricle (LV) 
      performance was evaluated with a pressure-volume microcatheter. Tumor necrosis 
      factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and monocyte chemoattractant 
      protein-1 (MCP-1) in the myocardium and plasma were assessed using enzyme-linked 
      immunosorbent assay. RESULTS: Sepsis reduced LV ejection fraction and cardiac 
      output in both young adult and old WT mice. However, identical CLP caused more 
      severe cardiac dysfunction and high mortality in old WT mice that were 
      accompanied by greater levels of TNF-alpha, IL-1beta, IL-6 and MCP-1 in the myocardium 
      and plasma. TLR2 KO diminished aging-related difference in myocardial and 
      systemic inflammatory response, resulting in improved cardiac function and 
      decreased mortality in old septic mice. In addition, higher myocardial TLR2 
      levels in old WT mice resulted in greater myocardial inflammatory response and 
      worse cardiac dysfunction following administration of TLR2 agonist. CONCLUSION: 
      Moderate sepsis results in greater cardiac dysfunction and significant mortality 
      in old mice. Aging elevates TLR2 level/activity to exacerbate the inflammatory 
      response to sepsis, leading to worse cardiac dysfunction and mortality.
CI  - (c) 2023 Zhai, Yao, The, Ao, Fullerton and Meng.
FAU - Zhai, Yufeng
AU  - Zhai Y
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 - Ao, Lihua
AU  - Ao L
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
DEP - 20231129
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC10716470
OTO - NOTNLM
OT  - aging
OT  - cardiac dysfunction
OT  - mortality
OT  - myocardial TLR2
OT  - sepsis
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- 2023/12/14 06:42
MHDA- 2023/12/14 06:43
PMCR- 2023/01/01
CRDT- 2023/12/14 04:10
PHST- 2023/09/18 00:00 [received]
PHST- 2023/11/14 00:00 [accepted]
PHST- 2023/12/14 06:43 [medline]
PHST- 2023/12/14 06:42 [pubmed]
PHST- 2023/12/14 04:10 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2023.1293866 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2023 Nov 29;10:1293866. doi: 10.3389/fcvm.2023.1293866. 
      eCollection 2023.