5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction

Popp, Sandy; Schmitt-Böhrer, Angelika G.; Langer, Simon; Hofmann, Ulrich; Hommers, Leif; Schuh, Kai; Frantz, Stefan; Lesch, Klaus‐Peter; Frey, Anna

doi:10.3390/jcm10143104

Cited by 6 publications

(3 citation statements)

References 77 publications

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“…In support of this observation is a study demonstrating that expression of inflammatory cytokines can be upregulated in the myocardium of Sert -/mice after experimental myocardial infarction. By contrast, there were no differences observed in non-operated mice (50). Furthermore, it has been shown in a mouse model of chemically induced colitis that SERT deficiency can increase infiltration of inflammatory cells into the mucosa and submucosa (51).…”

Section: Discussionmentioning

confidence: 81%

Serotonin transporter-deficient mice display enhanced adipose tissue inflammation after chronic high-fat diet feeding

Hoch,

Burkhard,

Zhang

et al. 2023

Front. Immunol.

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IntroductionSerotonin is involved in leukocyte recruitment during inflammation. Deficiency of the serotonin transporter (SERT) is associated with metabolic changes in humans and mice. A possible link and interaction between the inflammatory effects of serotonin and metabolic derangements in SERT-deficient mice has not been investigated so far.MethodsSERT-deficient (Sert-/-) and wild type (WT) mice were fed a high-fat diet, starting at 8 weeks of age. Metabolic phenotyping (metabolic caging, glucose and insulin tolerance testing, body and organ weight measurements, qPCR, histology) and assessment of adipose tissue inflammation (flow cytometry, histology, qPCR) were carried out at the end of the 19-week high-fat diet feeding period. In parallel, Sert-/- and WT mice received a control diet and were analyzed either at the time point equivalent to high-fat diet feeding or as early as 8-11 weeks of age for baseline characterization.ResultsAfter 19 weeks of high-fat diet, Sert-/- and WT mice displayed similar whole-body and fat pad weights despite increased relative weight gain due to lower starting body weight in Sert-/-. In obese Sert-/- animals insulin resistance and liver steatosis were enhanced as compared to WT animals. Leukocyte accumulation and mRNA expression of cytokine signaling mediators were increased in epididymal adipose tissue of obese Sert-/- mice. These effects were associated with higher adipose tissue mRNA expression of the chemokine monocyte chemoattractant protein 1 and presence of monocytosis in blood with an increased proportion of pro-inflammatory Ly6C+ monocytes. By contrast, Sert-/- mice fed a control diet did not display adipose tissue inflammation.DiscussionOur observations suggest that SERT deficiency in mice is associated with inflammatory processes that manifest as increased adipose tissue inflammation upon chronic high-fat diet feeding due to enhanced leukocyte recruitment.

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Section: Discussionmentioning

confidence: 81%

Serotonin transporter-deficient mice display enhanced adipose tissue inflammation after chronic high-fat diet feeding

Hoch,

Burkhard,

Zhang

et al. 2023

Front. Immunol.

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“…Herein, following a 24-h incubation with 5-HTP, MMP14 and MMP2 , were downregulated by the 200 μM 5-HTP dose and tended to be upregulated by the 50 μM 5-HTP dose, respectively. Induced heart attack in 5-HTT (serotonin transporter) knock out models displayed an upregulated expression of MMP2 in the heart 43 . These authors postulate the 5-HT deficiency to be responsible for an impaired healing of the heart muscle.…”

Section: Discussionmentioning

confidence: 99%

In vitro effects of 5-Hydroxy-L-tryptophan supplementation on primary bovine mammary epithelial cell gene expression under thermoneutral or heat shock conditions

Field

Ouellet

Sheftel

et al. 2022

Sci Rep

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Serotonin (5-HT) is an autocrine-paracrine molecule within the mammary gland regulating homeostasis during lactation and triggering involution after milk stasis. Exposure of dairy cows to hyperthermia during the dry period alters mammary gland involution processes leading to reduced subsequent yields. Herein, primary bovine mammary epithelial cells (pBMEC) under thermoneutral (TN, 37 °C) or heat shock (HS, 41.5 °C) conditions were cultured with either 0, 50, 200, or 500 μM 5-Hydroxy-L-tryptophan (5-HTP; 5-HT precursor) for 8-, 12- or 24-h. Expression of 95 genes involved in 5-HT signaling, involution and tight junction regulation were evaluated using a Multiplex RT-qPCR BioMark Dynamic Array Circuit. Different sets of genes were impacted by 5-HTP or temperature, or by their interaction. All 5-HT signaling genes were downregulated after 8-h of HS and then upregulated after 12-h, relative to TN. After 24-h, apoptosis related gene, FASLG, was upregulated by all doses except TN-200 μM 5-HTP, and cell survival gene, FOXO3, was upregulated by HS-50, 200 and 500 μM 5-HTP, suggesting 5-HTP involvement in cell turnover under HS. Supplementing 5-HTP at various concentrations in vitro to pBMEC modulates the expression of genes that might aid in promoting epithelial cell turn-over during involution in dairy cattle under hyperthermia.

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“…Several genes have also been identi ed to be associated with MI, such as Nppa, Serpina3n, and Anxa1, which are signi cantly altered after MI [11]. Recent studies have shown that 5-HTT De ciency Affects Healing after Myocardial Infarction [12]. CTRP1 exacerbates cardiac dysfunction after myocardial infarction by regulating TLR4 in macrophages [13].…”

Section: Introductionmentioning

confidence: 99%

EPHB2 knockdown mitigated MI-induced myocardial injury by inhibiting MAPK signaling

Jiang¹,

Wang²,

Kang

2023

Preprint

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Myocardial infarction (MI) is a common disease in the cardiovascular field. The incidence of ventricular remodeling dysplasia and heart failure increases significantly after MI. The objective of this study was to investigate whether EPHB2 could regulate myocardial injury after MI and explore its regulatory pathways. RT-qPCR and Western blot were used to verify the expression of EPHB2 in MI mice, and then shRNA knockdown of EPHB2 was used to confirm the relationship between EPHB2 expression and disease progression. The levels of inflammation, apoptosis and fibrosis were detected by tissue staining. Related factors were detected by RT-qPCR, Western blot or ELISA. Further, the signaling pathway through which EPHB affected MI processes was detected and preliminarily confirmed by Western blot. EPHB2 was significantly overexpressed in heart tissue of MI mice. Knockdown of EPHB2 gene significantly downregulated immune factors and apoptotic factors, and alleviated mi-induced cardiac tissue damage and functional decline in mice. The MAPK pathway was found to be a downstream pathway in which EPHB2 acted. Knockdown EPHB2 down-regulates phosphorylation of MAPK pathway-related proteins. In mouse models, knockdown EPHB2 alleviated MI-induced cardiac function decline, inflammation and apoptosis of myocardial tissue, and myocardial fibrosis. This process may be achieved through the MAPK pathway.

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5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction

Cited by 6 publications

References 77 publications

Serotonin transporter-deficient mice display enhanced adipose tissue inflammation after chronic high-fat diet feeding

Serotonin transporter-deficient mice display enhanced adipose tissue inflammation after chronic high-fat diet feeding

In vitro effects of 5-Hydroxy-L-tryptophan supplementation on primary bovine mammary epithelial cell gene expression under thermoneutral or heat shock conditions

EPHB2 knockdown mitigated MI-induced myocardial injury by inhibiting MAPK signaling

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