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Original research
Elevation of ceramide and activation of secretory acid sphingomyelinase in patients with acute coronary syndromes Wei Pana, Jingjia Yub, Ruizheng Shia, Lei Yana, Tianlun Yanga, Yuanjian Lic, Zhuohua Zhangb, Guolong Yua, Yongping Baia, Edward H. Schuchmand, Xingxuan Hed and Guogang Zhanga Background Although there are several reported evidences for a pathogenic role of sphingolipid signaling in atherosclerosis, peripheral blood levels of ceramide and secretory acid sphingomyelinase (S-SMase) activity in patients with acute coronary syndromes (ACS) have not been evaluated. Methods and results A total of 304 CAD patients and 52 healthy individuals were divided into four groups: control group (n = 52), stable angina pectoris (SAP) group (n = 98), unstable angina pectoris (UAP) group (n = 92), and acute myocardial infarction (AMI) group (n = 114). Plasma levels of sphingomyelin (SPM) were elevated in patients with UAP and AMI compared with those in the control and SAP participants. Plasma ceramide levels and S-SMase activity in patients with ACS (including UAP and AMI) on day 0 were significantly higher than those in the control and SAP participants. Elevation in plasma ceramide levels in patients with UAP and AMI was sustained until a day after percutaneous coronary intervention or day 7, respectively. Moreover, in patients with UAP, S-SMase activity elevation on day 0 was followed by a gradual decrease toward the SAP range up to a day after
percutaneous coronary intervention. In patients with AMI, elevation in S-SMase activity showed a peak on day 3. Conclusion Serial changes in plasma ceramide and S-SMase activity were documented in patients with ACS. These findings provide an insight into the molecular mechanism of plaque destabilization. Coron Artery Dis c 2014 Wolters Kluwer Health | Lippincott 25:230–235 Williams & Wilkins. Coronary Artery Disease 2014, 25:230–235 Keywords: acute coronary syndromes, ceramide, matrix metalloproteinase, secretory acid sphingomyelinase, sphingomyelin, sphingomyelinase, tumor necrosis factor a Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, bThe State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, cDepartment of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China and d Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA
Correspondence to Guogang Zhang, MD, Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China Tel: + 86 731 84327695; fax: + 86 731 84327695; e-mail: [email protected] Received 13 October 2013 Revised 17 November 2013 Accepted 10 December 2013
Introduction
Materials and methods
Many studies have confirmed that sphingolipids, including sphingomyelin (SPM), secretory acid sphingomyelinase (S-SMase), and ceramide, are closely related to the development of atherosclerosis [1]. S-SMase, which can hydrolyze SPM into ceramide, plays a role in many pathological changes in the process of atherosclerosis, such as inducing apoptosis of smooth muscle cells, increasing aggregation of low-density lipoprotein (LDL), promoting the formation of foam cells, etc. [2]. However, the role played by these sphingolipids in acute coronary syndromes (ACS) is still not known.
Study participants and data collection
It is well known that the degradation of extracellular matrix and inflammatory response is involved in the progression of ACS [3]. Many studies have found that S-SMase can regulate the activation of matrix metalloproteinase and be induced by inflammatory factors. Therefore, we investigated the change in peripheral blood levels of ceramide and S-SMase activity in patients with ACS, including unstable angina pectoris (UAP) and acute myocardial infarction (AMI). c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0954-6928
The study was carried out between 2010 and 2012, consecutively enrolling 52 healthy individuals and 304 patients with chest pain, by the attending physician from the Department of Cardiovascular Medicine of Xiangya Hospital (Changsha, China). The stable angina pectoris (SAP) group included patients who complained of angina on effort without evidence of recent deterioration or pain at rest in the previous 6 months. The UAP group included patients who had angina pain at rest within the preceding 24 h before hospital presentation and new STsegment depression of more than 0.1 mV or transient ST-segment elevation (< 30 min) of more than 0.1 mV in at least two contiguous leads, without a cardiac troponin I (cTnI) higher than the upper limit of the normal range (excluding non-ST-segment elevation myocardial infarction). Patients with AMI were defined as those with the presence of typical prolonged chest pain accompanied by serial changes on the ECG and an increase (higher than the upper normal range) in cTnI. Only AMI patients who DOI: 10.1097/MCA.0000000000000079
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ceramide and S-ASMase elevated in ACS Pan et al. 231
were unsuitable for an emergency percutaneous coronary intervention (PCI) for admission to our hospital more than 12 h after symptom onset or for other reasons were enrolled. Key exclusion criteria included the presence of advanced renal failure (calculated as creatinine clearance
Original research
Elevation of ceramide and activation of secretory acid sphingomyelinase in patients with acute coronary syndromes Wei Pana, Jingjia Yub, Ruizheng Shia, Lei Yana, Tianlun Yanga, Yuanjian Lic, Zhuohua Zhangb, Guolong Yua, Yongping Baia, Edward H. Schuchmand, Xingxuan Hed and Guogang Zhanga Background Although there are several reported evidences for a pathogenic role of sphingolipid signaling in atherosclerosis, peripheral blood levels of ceramide and secretory acid sphingomyelinase (S-SMase) activity in patients with acute coronary syndromes (ACS) have not been evaluated. Methods and results A total of 304 CAD patients and 52 healthy individuals were divided into four groups: control group (n = 52), stable angina pectoris (SAP) group (n = 98), unstable angina pectoris (UAP) group (n = 92), and acute myocardial infarction (AMI) group (n = 114). Plasma levels of sphingomyelin (SPM) were elevated in patients with UAP and AMI compared with those in the control and SAP participants. Plasma ceramide levels and S-SMase activity in patients with ACS (including UAP and AMI) on day 0 were significantly higher than those in the control and SAP participants. Elevation in plasma ceramide levels in patients with UAP and AMI was sustained until a day after percutaneous coronary intervention or day 7, respectively. Moreover, in patients with UAP, S-SMase activity elevation on day 0 was followed by a gradual decrease toward the SAP range up to a day after
percutaneous coronary intervention. In patients with AMI, elevation in S-SMase activity showed a peak on day 3. Conclusion Serial changes in plasma ceramide and S-SMase activity were documented in patients with ACS. These findings provide an insight into the molecular mechanism of plaque destabilization. Coron Artery Dis c 2014 Wolters Kluwer Health | Lippincott 25:230–235 Williams & Wilkins. Coronary Artery Disease 2014, 25:230–235 Keywords: acute coronary syndromes, ceramide, matrix metalloproteinase, secretory acid sphingomyelinase, sphingomyelin, sphingomyelinase, tumor necrosis factor a Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, bThe State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, cDepartment of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China and d Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA
Correspondence to Guogang Zhang, MD, Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China Tel: + 86 731 84327695; fax: + 86 731 84327695; e-mail: [email protected] Received 13 October 2013 Revised 17 November 2013 Accepted 10 December 2013
Introduction
Materials and methods
Many studies have confirmed that sphingolipids, including sphingomyelin (SPM), secretory acid sphingomyelinase (S-SMase), and ceramide, are closely related to the development of atherosclerosis [1]. S-SMase, which can hydrolyze SPM into ceramide, plays a role in many pathological changes in the process of atherosclerosis, such as inducing apoptosis of smooth muscle cells, increasing aggregation of low-density lipoprotein (LDL), promoting the formation of foam cells, etc. [2]. However, the role played by these sphingolipids in acute coronary syndromes (ACS) is still not known.
Study participants and data collection
It is well known that the degradation of extracellular matrix and inflammatory response is involved in the progression of ACS [3]. Many studies have found that S-SMase can regulate the activation of matrix metalloproteinase and be induced by inflammatory factors. Therefore, we investigated the change in peripheral blood levels of ceramide and S-SMase activity in patients with ACS, including unstable angina pectoris (UAP) and acute myocardial infarction (AMI). c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0954-6928
The study was carried out between 2010 and 2012, consecutively enrolling 52 healthy individuals and 304 patients with chest pain, by the attending physician from the Department of Cardiovascular Medicine of Xiangya Hospital (Changsha, China). The stable angina pectoris (SAP) group included patients who complained of angina on effort without evidence of recent deterioration or pain at rest in the previous 6 months. The UAP group included patients who had angina pain at rest within the preceding 24 h before hospital presentation and new STsegment depression of more than 0.1 mV or transient ST-segment elevation (< 30 min) of more than 0.1 mV in at least two contiguous leads, without a cardiac troponin I (cTnI) higher than the upper limit of the normal range (excluding non-ST-segment elevation myocardial infarction). Patients with AMI were defined as those with the presence of typical prolonged chest pain accompanied by serial changes on the ECG and an increase (higher than the upper normal range) in cTnI. Only AMI patients who DOI: 10.1097/MCA.0000000000000079
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ceramide and S-ASMase elevated in ACS Pan et al. 231
were unsuitable for an emergency percutaneous coronary intervention (PCI) for admission to our hospital more than 12 h after symptom onset or for other reasons were enrolled. Key exclusion criteria included the presence of advanced renal failure (calculated as creatinine clearance
