Sage Journals: Discover world-class research

Abstract

Background/Aim:

In addition to its cholesterol-lowering effect, atorvastatin (ATV) has been thought to have multiple cardiovascular benefits, including anti-inflammatory and anti-apoptotic properties. The present study was undertaken to determine whether ATV pretreatment could attenuate myocardial apoptosis and inflammation and improve cardiac function in a swine model of coronary microembolization (CME).

Methods:

Twenty-four swine were randomly and equally divided into a sham-operated (control) group, CME group, and CME plus ATV group. Swine CME was induced by intracoronary injection of inert plastic microspheres (diameter 42 μm) into the left anterior descending coronary, with or without pretreatment of ATV. Echocardiographic measurements, a pathological examination, terminal deoxynucleotidyl transferase–mediated nick end labeling staining, and Western blotting were performed to assess the functional, morphological, and molecular effects in CME.

Results:

The expression levels of caspase 3 and tumor necrosis factor-α (TNF-α) were aberrantly upregulated in cardiomyocytes following CME. Downregulation of caspase 3 and TNF-α with ATV pretreatment was associated with improved cardiac function and attenuated serum cardiac troponin I (cTnI) and high-sensitivity C-reactive protein. In addition, through a Pearson correlation analysis, the left ventricular ejection fraction negatively correlated with caspase 3, TNF-α, and cTnI.

Conclusion:

This study demonstrated that ATV pretreatment could significantly inhibit CME-induced myocardial apoptosis and inflammation and improve cardiac function. The data generated from this study provide a rationale for the development of myocardial apoptosis and inflammation-based therapeutic strategies for CME-induced myocardial injury.

Keywords

coronary microembolization inflammation apoptosis atorvastatin

Introduction

Coronary microembolization (CME), which can be induced by either a spontaneous rupture of a vulnerable coronary atherosclerotic plaque or therapeutic percutaneous coronary interventions (PCIs), has been found to be associated with adverse outcomes such as cardiac contractile dysfunction and reduced coronary reserve.^1,2 The typical consequences of CME include microinfarcts with an inflammatory response, contractile dysfunction, and reduced coronary reserve.³ Coronary vasodilators protect against microembolization when their administration is initiated prior to PCIs. Distal protection devices can retrieve atherothrombotic debris and prevent its embolization into the microcirculation, but their effect on clinical outcome has been disappointing so far, except for saphenous vein bypass grafts.⁴ Because of the grave consequences of CME, many investigations have sought to determine the underlying mechanisms of CME-induced myocardial injury and alleviate the deleterious effects of CME. There have been major advances in identifying factors of the myocardial inflammatory response and apoptosis that are involved in CME-induced myocardial injury, but the overall complexity of myocardial injury suggests that additional regulatory mechanisms remain to be elucidated.^5,6 Our previous studies demonstrated that cardiomyocyte inflammation and apoptosis played a vital role in the mechanism of CME-induced myocardial injury.^7

-12 Additionally, a previous study by Herrmann et al¹³ showed the beneficial effect of statin against periprocedural CME. Furthermore, results of our recent studies revealed that atorvastatin (ATV) could lower the extent of myocardial injury after CME and improve cardiac function in mice, primarily through regulation of cardiomyocyte apoptosis,^7,14 although the potential molecular mechanisms remained unclear.

The aim of the present study was to determine the role of ATV pretreatment in CME-induced myocardial inflammation and apoptosis. In this study, we focused on the interactions of ATV with the proinflammatory protein tumor necrosis factor-α (TNF-α) and the proapoptotic protein caspase 3 in CME-induced myocardial inflammation and apoptosis. This study demonstrated that ATV pretreatment could significantly inhibit CME-induced myocardial apoptosis and inflammation and improve cardiac function. The data generated from this study provide a rationale for the development of myocardial apoptosis and inflammation-based therapeutic strategies for CME-induced myocardial injury.

Materials and Methods

Animal Preparation and Experimental Procedures

Healthy swine (25-30 kg) were purchased from the Animal Center of the Agriculture College of Guangxi University (Nanning, People’s Republic of China), and throughout all experimental stages, the animals were under controlled conditions of temperature, humidity, and light, with pig feed and water provided ad libitum. This investigation conforms to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication No. 85-23, revised 1996). The Clinical and Animal Research Ethics Committees of Guangxi Medical University approved all procedures.

Modeling and Grouping

Twenty-four miniature swine were randomly assigned into 3 groups, including a sham-operated (control) group, CME group, and CME plus ATV (ATV) group, with 8 swine in each group. The ATV group was pretreated with ATV for 7 days (2.5 mg/kg/d) and a high loading dose of ATV (80 mg) 30 minutes before microsphere injection. The CME model was induced by manual unremitting injection of microspheres into the left anterior descending (LAD) artery, as previously described by Dorge et al,¹⁵ Breuckmann et al,¹⁶ and Carlsson et al.¹⁷ The swine were initially sedated via an intramuscular injection of ketamine and atropine (10-15 mg/kg and 2 mg, respectively). After endotracheal intubation, anesthesia was maintained via an intravenous drip of diazepam into the ear vein. The right femoral artery was separated, and a 6F (Cordis Corporation, USA) vascular sheath was placed. Prior to the coronary cannulation, the animals were anticoagulated via an intravenous injection of 200 U/kg heparin followed by 100 U/kg/h to maintain heparinization. A 6F JL 4.0 guiding catheter was used for the coronary angiography. After the coronary angiography, a 1.8F infusion catheter (Cordis) was placed into the LAD artery, with the tip located between the second and third diagonal branches. Microspheres with a diameter of 42 μm (Dynospheres; Dyno Particles, Lillestrøm, Norway) at a mean dosage of 100 000 were selectively infused into the LAD within 40 minutes followed by a flush with 10 mL of saline. The sham-operated swine (sham group) were subjected to the same procedures, except that the injection was saline rather than microspheres. The systemic blood pressure and heart rate were continuously monitored during the procedure.

Statistical Analysis

All quantitative data are expressed as the means (standard deviation) and were analyzed using the SPSS 13.0 software. Two-tailed, unpaired Student t tests, 1-way analysis of variance, and Pearson correlation analysis were used for statistical evaluation of the data. Differences were considered statistically significant when P < .05.

Results

Animal Groups

No significant differences in the body weight or heart rate were observed among the 4 groups (Supplemental Table S1).

ATV Pretreatment Improved Cardiac Function Following CME

Results of echocardiographic examination (Table 1) showed that 12 hours after CME modeling, the CME group exhibited significantly decreased cardiac systolic function compared with the control group, as indicated by significantly reduced left ventricular ejection fraction (LVEF), fractional shortening, and cardiac output as well as increased left ventricular end-diastolic diameter in the CME group (P < .05). Additionally, ATV pretreatment was associated with improved cardiac function in the CME swine.

Table 1.

Effect of Atorvastatin on Cardiac Function Following CME.^a

Groups	LVEF, %	FS, %	LVEDd, mm	CO, L/min	LVESD, mm	LVEDV, mL	LVESV, mL
Control	68.72 ± 2.79	43.28 ± 2.58	31.75 ± 2.63	4.21 ± 0.32	10.36 ± 1.68	31.86 ± 2.35	1.23 ± 0.29
CME	49.73 ± 5.23^b	24.69 ± 3.64^b	40.35 ± 2.43^b	2.54 ± 0.22^b	20.28 ± 2.26^b	66.24 ± 3.26^b	8.32 ± 1.82^b
ATV	60.24 ± 2.63^c	32.29 ± 2.58^c	36.21 ± 2.54^c	3.53 ± 0.29^c	14.40 ± 1.89^c	47.52 ± 2.89^c	3.08 ± 1.24^c

Abbreviations: ATV, atorvastatin; CME, coronary microembolization; CO, cardiac output; FS, fractional shortening; LVEDd, left ventricular end-diastolic diameter; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; LVESV, left ventricular end-systolic volume; PTEN, phosphatase and tensin homolog deleted on chromosome 10. Sham: sham group; CME: CME group; ATV: CME + ATV group.

^aData are presented as the mean (SD).

^b P < .05 compared with sham.

^c P < .05 compared with CME.

ATV Pretreatment Attenuated Myocardial Injury Marker Following CME

Myocardial injury following CME could be assessed by levels of cardiac troponin I (cTnI) in blood obtained from the coronary sinus (Figure 1). At 12 hours after CME modeling, serum levels of cTnI in swine from the CME group were higher than the control group (0.207 [0.016] μg/L vs 0.053 [0.009] μg/L, P = .018). Moreover, ATV pretreatment attenuated myocardial injury following CME, as reflected by the reduced cTnI levels in the ATV group compared with the CME group (0.104[0.016] μg/L vs 0.207[0.016] μg/L, P = .037).

Figure 1.

Atorvastatin (ATV) pretreatment attenuated the myocardial injury marker following coronary microembolization (CME). Serum cardiac troponin I expression was significantly increased in the CME group compared with that of the sham group (P < .05). The administration of ATV reduced the cTnI level. ^a P < .05 versus sham; ^b P < .05 versus CME. N = 8 for each group. Mean ± standard deviation. Sham: sham group; CME: CME group; ATV: CME + ATV group.

ATV Pretreatment Attenuated Inflammation Markers Following CME

The myocardial inflammatory response following CME could be assessed by measuring the levels of high-sensitivity C-reactive protein (hs-CRP) in the blood obtained from the coronary sinus (Figure 2). At 12 hours after CME modeling, serum levels of hs-CRP in swine from the CME group were higher than the control (4.58 [1.23] mg/L vs 0.56 [0.23] mg/L, P = .015). Moreover, ATV pretreatment attenuated the myocardial inflammatory response following CME, as reflected by the reduced hs-CRP levels in the ATV group compared with the CME group (2.16[0.86] mg/L vs 4.58 [1.23] mg/L, P = .042).

Figure 2.

Atorvastatin (ATV) pretreatment attenuated the inflammation marker following coronary microembolization (CME). Serum high-sensitivity C-reactive protein (hs-CRP) expression was significantly increased in the CME group compared with that of the sham group (P < .05). The administration of ATV reduced the hs-CRP level. ^a P < .05 versus sham; ^b P < .05 versus CME. N = 8 for each group. Mean ± standard deviation. Sham: sham group; CME: CME group; ATV: CME + ATV group.

CME Histopathology

As revealed by Mayer hematoxylin and eosin (Figure S1A, B) and hematoxylin-basic fuchsin-picric acid (HBFP) staining (Figure S2A, B), the control animals exhibited subendocardial ischemia without infarction foci, whereas the CME animals exhibited multiple microinfarction foci. The administration of ATV reduced the microinfarct volume and inflammatory cell infiltration. The HBFP staining revealed myocardial karyolysis or hypochromatosis based on the red cytoplasmic staining of the microinfarction foci. In addition, peripheral cardiac muscle edema and denaturation, peripheral inflammatory cell infiltration, and erythrocyte effusion were detected. For each group, the infarct area was sham 0.00 (0.00)%, CME 6.24 (2.85)%, and ATV 3.45 (2.52)%, P = .023. (Figure S2C)

ATV Pretreatment Decreased Myocardial Apoptosis Following CME

Myocardial apoptosis was assessed using terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Compared with the control group, more TUNEL-positive (brown) cardiomyocytes could be detected in swine from the CME groups (Figure S3A). Interestingly, ATV treatment significantly decreased the relative proportion of apoptotic cells following CME (Figure S3B). The percentages of myocardial apoptotic cells in the control, CME, and ATV were 0.32(0.18), 8.93(1.58), and 4.56(1.23), P = .032, respectively (Figure S3C).

ATV Pretreatment Inhibited Myocardial TNF-α and Caspase 3 in CME Swine

Western blotting showed significant upregulation of caspase 3 (Figure 3) and TNF-α (Figure 4) proteins following CME modeling compared with those from the control group (P < .05). However, ATV pretreatment was associated with reduced levels of TNF-α and caspase 3 proteins compared with the CME group (P < .05).

Figure 3.

Effect of atorvastatin (ATV) on caspase 3 expression after coronary microembolization (CME). The relative protein level of cleaved caspase 3 was determined by Western blot, and the ratio of caspase 3 IA to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) IA was used to represent the relative level of caspase 3. ^a P < .05 versus sham; ^b P < .05 versus CME. N = 8 for each group. Mean ± standard deviation. Sham: sham group; CME: CME group; ATV: CME + ATV group.

Figure 4.

Effect of atorvastatin (ATV) on tumor necrosis factor-α (TNF-α) expression after coronary microembolization (CME). The relative protein level of TNF-α was determined by Western blot, and the ratio of TNF-αIA to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) IA was used to represent the relative level of TNF-α. ^a P < .05 versus sham; ^b P < .05 versus CME. N = 8 for each group. Mean ± standard deviation. Sham: sham group; CME: CME group; ATV: CME + ATV group.

Pearson Correlation Analysis

Using a Pearson correlation analysis, the LVEF negatively correlated with caspase 3 (r = −.937, P < .001), TNF-α (r = −.852, P < .001), and cTnI (r = −.906, P < .001; Figure 5).

Figure 5.

Pearson correlation analysis. Using a Pearson correlation analysis, the left ventricular ejection fraction (LVEF) negatively correlated with caspase 3 (r = −.937, P < .001), tumor necrosis factor-α (TNF-α; r = −.852, P < .001), and cardiac troponin I (cTnI; r = −.906, P < .001).

Discussion

The novel findings of the present study are summarized as follows. First, we demonstrated that the expression levels of caspase 3 and TNF-α were aberrantly upregulated in cardiomyocytes following CME. Second, downregulation of caspase 3 and TNF-α with ATV pretreatment was associated with improved cardiac function and attenuated cTnI and hs-CRP levels. These findings not only help us understand the mechanisms by which myocardial apoptosis and inflammation mediate myocardial injury but also support our hypothesis that TNF-α and caspase 3 proteins may represent 2 potential intervention targets. The data generated from this study provide a rationale for the development of myocardial apoptosis and inflammation-based therapeutic strategies for CME-induced myocardial injury.

Coronary microembolization is widely observed in acute coronary syndrome and is considered to be an iatrogenic complication following coronary interventions in clinical settings.⁴ Coronary microembolization, caused by the embolization of thrombotic material and debris or the rupture of an atherosclerotic plaque, is believed to generate a transient decrease in coronary blood flow, followed by reactive hyperemia and myocardial systolic dysfunction. Rioufol et al¹⁸ demonstrated that the formation of atherosclerosis frequently presented with the rupture and repair of plaques. Therefore, our data further confirm the pathophysiological manifestations of CME.

Previous studies demonstrate that the aggregate amount of infarction involved a small area (<5%) in the microembolized myocardium of pigs or dogs, as indicated by typical inflammatory responses, including increased TNF-α expression and leukocyte infiltration.^19

-22 Additionally, our previous studies demonstrated that an intense inflammatory response triggered by CME increases the protein level of TNF-α in cardiomyocytes.⁹ Furthermore, our previous study revealed that cardiomyocyte apoptosis plays a significant role in CME-induced myocardial injury and that the expression of the proapoptotic protein caspase 3 in cardiomyocytes was elevated.¹⁰

Atorvastatin had been proposed to have multiple cardiovascular benefits besides its cholesterol-lowering effect, including anti-inflammatory and antiapoptotic properties. In recent years, many studies validated its antiapoptotic effect in animal models of myocardial ischemia and reperfusion injury,⁴ coronary atherosclerosis,²³myocardial infarction,^5,24 and renal ischemia–reperfusion injury.²⁵ Additional studies have shown that ATV may regulate the mitochondrial apoptotic pathway and the inflammatory pathway. Caspases are a family of aspartic acid–specific proteases that have been considered to be key in the induction of apoptosis.²⁶ Caspase 3 is an initiator caspase in the mitochondrial apoptosis cascade.²⁶ Tumor necrosis factor-α is the most critical factor in inflammatory reaction pathways. Atorvastatin has been shown to modulate the cellular immune balance between activation and negative regulation of cells, thereby inhibiting expression of the proinflammatory factor TNF-α.²⁷Atorvastatin could inhibit activation of the cell apoptotic signaling pathway.^28,29 In view of the aforementioned findings, we proposed that pretreatment of ATV in CME animals may protect against CME-related myocardial dysfunction by the blockade of the mitochondrial apoptotic pathway and the inflammatory pathway. In this study, we found that pretreatment with ATV (2.5 mg/kg/d) for 7 days was associated with substantially reduced myocardial apoptosis and inflammation and also preserved myocardial function. These results suggest that ATV can reduce CME-induced myocardial injury through inhibiting myocardial apoptosis and inflammation.

In summary, we revealed the important role of cardiac-specific caspase 3 and TNF-α in the CME-induced myocardial apoptosis and inflammation. The results of this study highlight the potential of caspase 3 and TNF-α as interventional targets for the treatment of CME-related myocardial apoptosis and inflammation. Moreover, the potential therapeutic role of ATV seems to have regulatory effects on the mitochondrial apoptotic pathway and the inflammatory pathway. It should be noted that our research was performed in swine models, and the findings may not be extrapolated directly to humans. Further research, especially translational research in humans, is needed to evaluate whether the potential regulatory effects of ATV on caspase 3 and TNF-α pathways could lead to a promising treatment strategy for CME-related cardiac dysfunction.

Footnotes

Author Contributions

Jiang-You Wang contributed to conception and design; contributed to acquisition, analysis, and interpretation; critically revised manuscript; and agrees to be accountable for all aspects of work ensuring integrity and accuracy. Han Chen contributed to conception and contributed to analysis and interpretation. Xi Su contributed to conception, contributed to acquisition, and drafted the manuscript. You Zhou contributed to design, contributed to analysis, and drafted the manuscript. Lang Li contributed to conception and design; contributed to acquisition, analysis, and interpretation and agrees to be accountable for all aspects of work ensuring integrity and accuracy.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by a grant from the National Natural Science Foundation of China (Grant No 81260042).

Supplemental Material

The online supplemental figures and tables are available at .

References

Heusch

Kleinbongard

Bose

. Coronary microembolization: from bedside to bench and back to bedside. Circulation. 2009;120(18):1822–1836.

Otto

Seeber

Fujita

. Microembolization and myonecrosis during elective percutaneous coronary interventions in diabetic patients: an intracoronary Doppler ultrasound study with 2-year clinical follow-up. Basic Res Cardiol. 2012;107(5):289.

Skyschally

Schulz

Erbel

Heusch

. Reduced coronary and inotropic reserves with coronary microembolization. Am J Physiol Heart Circ Physiol. 2002;282(2):H611–H614.

Skyschally

Walter

Heusch

. Coronary microembolization during early reperfusion: infarct extension, but protection by ischaemic postconditioning. Eur Heart J. 2013;34(42):3314–3321.

Dorge

Schulz

Belosjorow

. Coronary microembolization: the role of TNF-alpha in contractile dysfunction. J Mol Cell Cardiol. 2002;34(1):51–62.

Zhang

Chen

. Mast cell contributes to cardiomyocyte apoptosis after coronary microembolization. J Histochem Cytochem. 2006;54(5):515–523.

Wang

. Effect of atorvastatin (Lipitor) on myocardial apoptosis and caspase-8 activation following coronary microembolization. Cell Biochem Biophys. 2011;61(2):399–406.

Liu

Zhou

Wen

. Effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization in rats. Exp Clin Cardiol. 2013;18(2):161–165.

Wen

Huang

. The role of ERK1/2 signaling pathway in coronary microembolization-induced rat myocardial inflammation and injury. Cardiology. 2010;117(3):207–215.

10.

Wang

Chen

Zhou

Liu

. The PTEN/Akt signaling pathway mediates myocardial apoptosis in swine after coronary microembolization. J Cardiovasc Pharmacol Ther. 2016;21(5):471–477.

11.

Liu

Zhou

Wang

. Coronary microembolization induces cardiomyocyte apoptosis in swine by activating the LOX-1-dependent mitochondrial pathway and caspase-8-dependent pathway. J Cardiovasc Pharmacol Ther. 2016;21(2):209–218.

12.

Liu

Zhou

Liu

. Coronary microembolization induces cardiomyocyte apoptosis through the LOX-1-dependent endoplasmic reticulum stress pathway involving JNK/P38 MAPK. Can J Cardiol. 2015;31(10):1272–1281.

13.

Herrmann

Lerman

Baumgart

. Preprocedural statin medication reduces the extent of periprocedural non-Q-wave myocardial infarction. Circulation. 2002;106(17):2180–2183.

14.

Wang

Chen

Zhou

. Atorvastatin inhibits myocardial apoptosis in a swine model of coronary microembolization by regulating PTEN/PI3K/Akt signaling pathway. Cell Physiol Biochem. 2016;38(1):207–219.

15.

Dorge

Neumann

Behrends

. Perfusion-contraction mismatch with coronary microvascular obstruction: role of inflammation. Am J Physiol Heart Circ Physiol. 2000;279(6):H2587–H2592.

16.

Breuckmann

Nassenstein

Bucher

. Systematic analysis of functional and structural changes after coronary microembolization: a cardiac magnetic resonance imaging study. JACC Cardiovasc Imaging. 2009;2(2):121–130.

17.

Carlsson

Wilson

Martin

Saeed

.Myocardial microinfarction after coronary microembolization in swine: MR imaging characterization. Radiology. 2009;250(3):703–713.

18.

Rioufol

Gilard

Finet

Ginon

Boschat

André-Fouët

. Evolution of spontaneous atherosclerotic plaque rupture with medical therapy: long-term follow-up with intravascular ultrasound. Circulation. 2004;110(18):2875–2880.

19.

Thielmann

Dorge

Martin

. Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine. Circ Res. 2002;90(7):807–813.

20.

Skyschally

Schulz

Gres

. Coronary microembolization does not induce acute preconditioning against infarction in pigs—the role of adenosine. Cardiovasc Res. 2004;63(2):313–322.

21.

Arras

Strasser

Mohri

. nr-alpha is expressed by monocytes/macrophages following cardiac microembolization and is antagonized by cyclosporine. Basic Res Cardiol. 1998;93(2):97–107.

22.

Skyschally

Gres

Hoffmann

. Bidirectional role of tumor necrosis factor-alpha in coronary microembolization: progressive contractile dysfunction versus delayed protection against infarction. Circ Res. 2007;100(1):140–146.

23.

Cui

. Inhibitory effect of atorvastatin on AGE-induced HCAEC apoptosis by upregulating HSF-1 protein. Int J Biol Macromol. 2013;57:259–264.

24.

Tang

Sanganalmath

Sato

. Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction. PLoS One. 2011;6(9):e25320.

25.

Haylor

Harris

Nicholson

Waller

Huang

Yang

. Atorvastatin improving renal ischemia reperfusion injury via direct inhibition of active caspase-3 in rats. Exp Biol Med (Maywood). 2011;236(6):755–763.

26.

Holleyman

Larson

. Apoptosis in the ischemic reperfused myocardium. Perfusion. 2001;16(6):491–502.

27.

Tawfik

Ghattas

Abo-Elmatty

Abdel-Aziz

. Atorvastatin restores the balance between pro-inflammatory and anti-inflammatory mediators in rats with acute myocardial infarction. Eur Rev Med Pharmacol Sci. 2010;14(6):499–506.

28.

Hausenloy

Yellon

. New directions for protecting the heart against ischaemia-reperfusion injury: targeting the reperfusion injury salvage kinase (RISK)-pathway. Cardiovasc Res. 2004;61(3):448–460.

29.

Mensah

Mocanu

Yellon

. Failure to protect the myocardium against ischemia/reperfusion injury after chronic atorvastatin treatment is recaptured by acute atorvastatin treatment: a potential role for phosphatase and tensin homolog deleted on chromosome ten? J Am Coll Cardiol. 2005;45(8):1287–1291.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.38 MB

Atorvastatin Pretreatment Inhibits Myocardial Inflammation and Apoptosis in Swine After Coronary Microembolization

Abstract

Background/Aim:

Methods:

Results:

Conclusion:

Keywords

Introduction

Materials and Methods

Animal Preparation and Experimental Procedures

Modeling and Grouping

Statistical Analysis

Results

Animal Groups

ATV Pretreatment Improved Cardiac Function Following CME

ATV Pretreatment Attenuated Myocardial Injury Marker Following CME

ATV Pretreatment Attenuated Inflammation Markers Following CME

CME Histopathology

ATV Pretreatment Decreased Myocardial Apoptosis Following CME

ATV Pretreatment Inhibited Myocardial TNF-α and Caspase 3 in CME Swine

Pearson Correlation Analysis

Discussion

Footnotes

Author Contributions

Declaration of Conflicting Interests

Funding

Supplemental Material

References

Supplementary Material