Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction

Hortmann, Marcus; Robinson, Samuel D.; Mohr, M.; Haenel, David; Mauler, Maximilian; Stallmann, Daniela; Reinoehl, Joel; Duerschmied, Daniel; Peter, Karlheinz; Bode, Christoph; Ahrens, Ingo

doi:10.1016/j.ijcard.2017.05.088

Cited by 8 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study demonstrated the release of HtrA2 into the serum of STEMI patients [18]. If validated in vitro and in vivo, extracellular HtrA2 could have potential as a biomarker for apoptosis; however, in our results necrosis also caused the release of HtrA2.…”

Section: Discussioncontrasting

confidence: 46%

“…Although there is rapid progress in the treatment of myocardial ischemia, more than one third of STEMI patients do not show complete reperfusion due to severe IR injury [24,25]. Growing evidence indicates that HtrA2, a pro-apoptotic protein, is associated with myocardial reperfusion injury [14,15,16,17,18,26] and that targeted anti-apoptotic treatments may improve clinical outcomes in patients with ischemic heart disease [27].…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, HtrA2 has been shown to be significantly increased in serum of patients with ST-segment elevation myocardial infarction (STEMI) and shows promise as a potential biomarker for IR-injury. [18].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Extracellular HtrA2 Induces Apoptosis in Human Umbilical Vein Endothelial Cells

Kaur

Stallmann

Schanze

et al. 2019

IJMS

View full text Add to dashboard Cite

The serine protease high-temperature-required protein A2 (HtrA2) has been identified as a key intracellular molecule promoting apoptosis in cells during ischemia reperfusion (IR) injury. IR injury in ST-segment elevation myocardial infarction (STEMI) contributes to overall myocardial damage. HtrA2 has further been shown to be significantly increased in the serum of patients with STEMI. In the present pilot study, we use human umbilical vein endothelial cells (HUVECs) to investigate whether extracellular HtrA2 induces apoptosis using Annexin V staining. Furthermore, we examine whether HtrA2 is released extracellularly after staurosporine-induced apoptosis using ELISA. We find that HtrA2 is released upon induction of apoptosis by staurosporine into the cell culture medium. Furthermore, treatment of HUVECs with extracellular HtrA2-induces apoptosis, while the addition of anti-HtrA2 antibodies reduces both HtrA2- and staurosporine-induced endothelial cell apoptosis. In conclusion, we show here that extracellular HtrA2 induces apoptosis in human endothelial cells, although the exact molecular mechanisms have to be investigated in future.

show abstract

Section: Discussioncontrasting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular HtrA2 Induces Apoptosis in Human Umbilical Vein Endothelial Cells

Kaur

Stallmann

Schanze

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…LDH and CK-MB activities were expressed in U/L. Blood samples were obtained 24 h after MI, and serum cTnT levels were measured (pg/ml) using a commercial assay kit (ab246529, Cambridge MA, United States) according to the manufacturer's instructions, as described previously (Hortmann et al, 2017).…”

Section: Measurement Of Serum Lactatementioning

confidence: 99%

The Protective Effects of Shengmai Formula Against Myocardial Injury Induced by Ultrafine Particulate Matter Exposure and Myocardial Ischemia are Mediated by the PI3K/AKT/p38 MAPK/Nrf2 Pathway

Chen

Guo

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Background and Purpose: Ultrafine particulate matter (UFPM) induces oxidative stress (OS) and is considered to be a risk factor of myocardial ischemia (MI). Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties and has been used to treat cardiovascular diseases for a long time. The aim of this study was to explore the protective role of SMF and the mechanism by which it prevents myocardial injury in UFPM-exposed rats with MI.Methods: An MI rat model was established. Animals were randomly divided into five groups: sham, UFPM + MI, SMF (1.08 mg/kg⋅d) + UFPM + MI, SMF (2.16 mg/kg⋅d) + UFPM + MI, and SMF (4.32 mg/kg⋅d) + UFPM + MI. SMF or saline was administrated 7 days before UFPM instillation (100 μg/kg), followed by 24 h of ischemia. Physiological and biochemical parameters were measured, and histopathological examinations were conducted to evaluate myocardial damage. We also explored the potential mechanism of the protective role of SMF using a system pharmacology approach and an in vitro myoblast cell model with small molecule inhibitors.Results: UFPM produced myocardial injuries on myocardial infarct size; serum levels of LDH, CK-MB, and cardiac troponin; and OS responses in the rats with MI. Pretreatment with SMF significantly attenuated these damages via reversing the biomarkers. SMF also improved histopathology induced by UFPM and significantly altered the PI3K/AKT/MAPK and OS signaling pathways. The expression patterns of Cat, Gstk1, and Cyba in the UFPM model group were reversed in the SMF-treated group. In in vitro studies, SMF attenuated UFPM-induced reactive oxygen species production, mitochondrial damage, and OS responses. The PI3K/AKT/p38 MAPK/Nrf2 pathway was significantly changed in the SMF group compared with that in the UFPM group, whereas opposite results were obtained for pathway inhibition.Conclusion: These findings indicate that SMF prevents OS responses and exerts beneficial effects against myocardial injury induced by UFPM + MI in rats. Furthermore, the PI3K/AKT/p38 MAPK/Nrf2 signaling pathway might be involved in the protective effects of SMF.

show abstract

“…But on the other hand, mitochondria, as the major modifier of apoptosis, also play an important role in cardiomyocyte necrosis [ 7 ]. HtrA2, for example, a potential novel biomarker of mitochondrial associated reperfusion cardiomyocyte apoptosis and increased in patients with STEMI after percutaneous coronary intervention (PCI) [ 8 ]. Likewise, inflammation, thrombosis, and atherosclerosis (AS) participate in accelerating STEMI progression, and research has shown that serum sulfatides correlate positively with in-hospital mortality and complications in STEMI patients [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-206 may regulate mitochondrial ROS contribute to the progression of Myocardial infarction via TREM1

Lin,

Chu,

Yuan

et al. 2023

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Myocardial infarction (MI) is a leading cause of mortality. To better understand its molecular and cellular mechanisms, we used bioinformatic tools and molecular experiments to explore the pathogenesis and prognostic markers. Differential gene expression analysis was conducted using GSE60993 and GSE66360 datasets. Hub genes were identified through pathway enrichment analysis and PPI network construction, and four hub genes (AQP9, MMP9, FPR1, and TREM1) were evaluated for their predictive performance using AUC and qRT-PCR. miR-206 was identified as a potential regulator of TREM1. Finally, miR-206 was found to induce EC senescence and ER stress through upregulating mitochondrial ROS levels via TREM1. These findings may contribute to understanding the pathogenesis of MI and identifying potential prognostic markers.

show abstract

Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction

Cited by 8 publications

References 30 publications

Extracellular HtrA2 Induces Apoptosis in Human Umbilical Vein Endothelial Cells

Extracellular HtrA2 Induces Apoptosis in Human Umbilical Vein Endothelial Cells

The Protective Effects of Shengmai Formula Against Myocardial Injury Induced by Ultrafine Particulate Matter Exposure and Myocardial Ischemia are Mediated by the PI3K/AKT/p38 MAPK/Nrf2 Pathway

MiR-206 may regulate mitochondrial ROS contribute to the progression of Myocardial infarction via TREM1

Contact Info

Product

Resources

About