Beneficial effect of TLR4 blockade by a specific aptamer antagonist after acute myocardial infarction

Paz-García, Marta; Povo‐Retana, Adrián; Jaén, Rafael I.; Prieto, Patricia; Peraza, Diego A.; Zaragoza, Carlos; Hernández-Jiménez, Macarena; Piñeiro, David; Regadera, Javier; García‐Bermejo, Maria Laura; Rodríguez-Serrano, Esperanza Macarena; Sánchez-Garcí­a, Sergio; Moro, María A.; Lizasoaín, Ignacio; Delgado, Carmen; Valenzuela, Carmen

doi:10.1016/j.biopha.2023.114214

Cited by 9 publications

(12 citation statements)

References 72 publications

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“…However, a permanent or long-term inhibition of the TLR4 pathways will compromise not only the initial inflammatory responses but also proper and beneficial immune responses during the healing process ( 14 ). In a recent study in a rat model of cardiac I/R, a specific aptamer antagonist blocked TLR4 signaling after reperfusion and showed protective effects against cardiac injury 7 days post-MI ( 15 ), supporting the beneficial effects of targeting this pathway early after MI as shown in the present study by P7.…”

Section: Discussionsupporting

confidence: 86%

SLAMF1-derived peptide exhibits cardio protection after permanent left anterior descending artery ligation in mice

Olsen,

Kong,

Louwe

et al. 2024

Front. Immunol.

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Acute myocardial infarction (MI) results in tissue damage to affected areas of the myocardium. The initial inflammatory response is the most damaging for residual cardiac function, while at later stages inflammation is a prerequisite for proper healing and scar formation. Balancing the extent and duration of inflammation during various stages after MI is thus pivotal for preserving cardiac function. Recently, a signaling lymphocytic activation molecule 1 (SLAMF1)-derived peptide (P7) was shown to reduce the secretion of inflammatory cytokines and protected against acute lipopolysaccharide-induced death in mice. In the present study, we experimentally induced MI by permanent ligation of the left anterior descending artery (LAD) in mice and explored the beneficial effect of immediately administering P7, with the aim of dampening the initial inflammatory phase without compromising the healing and remodeling phase. Blood samples taken 9 h post-LAD surgery and P7 administration dampened the secretion of inflammatory cytokines, but this dampening effect of P7 was diminished after 3 days. Echocardiography revealed less deterioration of cardiac contraction in mice receiving P7. In line with this, less myocardial damage was observed histologically in P7-treated mice. In conclusion, the administration of a SLAMF1-derived peptide (P7) immediately after induction of MI reduces the initial myocardial inflammation, reduces infarct expansion, and leads to less deterioration of cardiac contraction.

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Section: Discussionsupporting

confidence: 86%

SLAMF1-derived peptide exhibits cardio protection after permanent left anterior descending artery ligation in mice

Olsen,

Kong,

Louwe

et al. 2024

Front. Immunol.

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show abstract

“…The TLR4/NF-κB pathway is thought to be the major signal transduction mechanism involved in cardiomyocyte apoptosis, a common process in many cardiovascular events 40 . Though the activation of TLR/NF-κB, particularly under exercise settings, has been related to two opposite roles, with some research proposing cardiac damage triggered by prolonged expression of inflammation 41 and others proposing cardiac-protective properties as it was shown that its upregulation is merely a participation in cardiac responses to physical exercise where its absence triggered myocardial injuries such as edema, hemorrhage, and inflammatory infiltration 39 . Even though all TLR signaling pathways culminate in activation of NF-κB, it remains unknown how TLR2/NF-κB is influenced when it comes to its cytokine’s expression in an exercise setting.…”

Section: Discussionmentioning

confidence: 99%

The role of TLR2 in exercise-induced immunomodulation in normal weight individuals

BAHMAN

ALSAEED

Al-Beloushi

et al. 2023

Sci Rep

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Toll-like receptors (TLRs) have been targeted for therapeutic drug development for several disorders, including cardiovascular diseases (CVD), and diabetes mellitus. Daily levels physical activity (PA) has been purported to influence the systemic circulation of cytokines, affecting the overall activation of TLRs and influencing the inflammatory milieu. Objective and self-reported daily PA was tracked in 69 normal-weight adults. Freedson's cut-offs categorized daily PA intensity into the 25th lowest, medium, and top percentiles. Monocytic TLR2 expression was quantified by flow cytometry in fresh whole blood. Cross-sectional associations between flow cytometry measured TLR2+ subsets and clinical biomarkers were evaluated. PA increased circulation of TLR2+ monocytes. TLR2 expression was adversely corelated with reduced diastolic blood pressure (DBP), triglyceride (TG), and matrix metallopeptidase 9 (MMP9) levels. However, regression analysis indicated that only TG levels were independently linked with TLR2+ subsets in circulation in active participants. Higher daily levels of physical activity are associated with improved cardiovascular blood markers and elevated circulatory monocytic TLR2+ subsets. These findings suggest that TLR2 may play a role in modulating CVD risk factors in individuals leading physically active lifestyles.

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“…The TLR4/NF-кB pathway is thought to be the major signal transduction mechanism involved in cardiomyocyte apoptosis, a common process in many cardiovascular events (34). Though the activation of TLR/NF-кB, particularly under exercise settings, has been related to two opposite roles, with some research proposing cardiac damage triggered by prolonged expression of in ammation (35) and others proposing cardiac-protective properties as it was shown that its upregulation is merely a participation in cardiac responses to physical exercise where its absence triggered myocardial injuries such as edema, hemorrhage, and in ammatory in ltration (33). Even though all TLR signaling pathways culminate in activation of NF-кB, it remains unknown how TLR2/NF-кB is in uenced when it comes to its cytokine's expression in an exercise setting.…”

Section: Discussionmentioning

confidence: 99%

The Role of TLR2 in Exercise-Induced Immunomodulation in normal weight individuals

BAHMAN

ALSAEED

Al-Beloushi

et al. 2023

Preprint

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Background Toll-like receptors (TLRs) have been targeted for therapeutic drug development for several disorders, including cardiovascular diseases, and diabetes mellitus. Daily levels physical activity (PA) has been purported to influence the systemic circulation of cytokines, affecting the overall activation of TLRs and influencing the inflammatory milieu.Methods Objective and self-reported daily PA was tracked in 69 normal-weight adults. Freedson's cut-offs categorized daily PA intensity into the 25th lowest, medium, and top percentiles. Monocytic TLR2 expression was quantified by flow cytometry in fresh whole blood. Cross-sectional associations between flow cytometry measured TLR2+ subsets and clinical biomarkers were evaluated.Results PA increased circulation of TLR2+ monocytes. TLR2 expression was adversely corelated with reduced diastolic blood pressure (DBP), triglyceride (TG), and matrix metallopeptidase 9 (MMP9) levels. However, regression analysis indicated that only TG levels were independently linked with TLR2+ subsets in circulation in active participants.Conclusions Higher daily PA levels improve cardiovascular health by upregulating monocytic TLR2+ subsets in circulation, indicating that TLR2 may modulate inflammatory cytokines under physically active lifestyles.

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Beneficial effect of TLR4 blockade by a specific aptamer antagonist after acute myocardial infarction

Cited by 9 publications

References 72 publications

SLAMF1-derived peptide exhibits cardio protection after permanent left anterior descending artery ligation in mice

SLAMF1-derived peptide exhibits cardio protection after permanent left anterior descending artery ligation in mice

The role of TLR2 in exercise-induced immunomodulation in normal weight individuals

The Role of TLR2 in Exercise-Induced Immunomodulation in normal weight individuals

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