Autotaxin inhibition reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction

Tripathi, Himi; Al-Darraji, Ahmed; Abo-Aly, Mohamed; Peng, Hsuan; Shokri, Elica; Chelvarajan, Lakshman; Donahue, Renée R.; Levitan, Bryana M.; Gao, Erhe; Hernandez, Gabriela; Morris, Andrew J.; Smyth, Susan S.; Abdel‐Latif, Ahmed

doi:10.1016/j.yjmcc.2020.09.011

Cited by 21 publications

(22 citation statements)

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“…The ATX induces inflammation through LPA, which is involved in maintaining vascular endothelial function, increasing vascular permeability, and vascular tone. 8,14,27 In addition, ATX promotes inflammation and fibrosis, resulting in organ remodelling. Furthermore, elevated serum ATX levels were observed in patients with sepsis, and a good correlation was observed between serum ATX and angiopoetin-2 levels (P < 0.001, Spearman's rank: 0.518).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the inhibitors suppressed increase in scar size, structural remodelling, and cardiac dysfunction. 14 LPA3 might be involved in myocardial hypertrophy and injury in rats, 32 and a deficiency of lipid phosphate phosphatase 3 (LPP3), which decomposes LPA3, might cause myocardial remodelling in mice. 33 In addition, suppression of LPA3 reportedly attenuated myocardial fibrosis, 34 and LPP3 knockout mice showed higher systemic and cardiac inflammation after AMI, decreased recovery of cardiac function, and increased remodelling and scar size.…”

Section: Discussionmentioning

confidence: 99%

“…33 In addition, suppression of LPA3 reportedly attenuated myocardial fibrosis, 34 and LPP3 knockout mice showed higher systemic and cardiac inflammation after AMI, decreased recovery of cardiac function, and increased remodelling and scar size. 14 In humans, an increase in plasma ATX and plasma LPA levels was observed after AMI, although the effect of ATX inhibitors on heart disease remains unclear. By contrast, ATX inhibitors have been investigated as new targets of treatment for IPF.…”

Section: Discussionmentioning

confidence: 99%

“…However, we could not find significant correlations between serum ATX levels and hsCRP or CVF in either sex, although ATX has been reported to be associated with inflammation and fibrosis. [12][13][14]…”

Section: Correlations Between Serum Autotaxin Levels and Other Variablesmentioning

confidence: 99%

“…8 In humans, a correlation between serum ATX levels and plasma BNP levels 13 and an increase in ATX and LPA levels was observed in patients with acute myocardial infarction (AMI). 14 Furthermore, high-ATX levels were reported to be a poor prognostic factor in patients with sepsis, a systemic inflammation. 15 However, little is known about the impact of ATX levels on future cardiac events in patients with NIDCM.…”

Section: Introductionmentioning

confidence: 99%

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Serum autotaxin as a novel prognostic marker in patients with non‐ischaemic dilated cardiomyopathy

et al. 2022

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Aims Autotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non-ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM. Methods and resultsWe enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high-ATX group and low-ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6-689.5) pg/mL vs. 96.5 (40.8-191.5) pg/mL, P = 0.010] were higher in the high-ATX group than low-ATX group, whereas high-sensitivity C-reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan-Meier survival analysis revealed that the event-free survival rate was significantly lower in the high-ATX group than low-ATX group (log-rank; P = 0.007). Cox proportional hazard analysis revealed that high-ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high-sensitivity C-reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048). Conclusion High serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM.

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Section: Discussionmentioning

confidence: 99%