Dataset Information

Clinical Evidence Supports a Protective Role for CXCL5 in Coronary Artery Disease.

ABSTRACT: Our goal was to measure the association of CXCL5 and molecular phenotypes associated with coronary atherosclerosis severity in patients at least 65 years old. CXCL5 is classically defined as a proinflammatory chemokine, but its role in chronic inflammatory diseases, such as coronary atherosclerosis, is not well defined. We enrolled individuals who were at least 65 years old and undergoing diagnostic cardiac catheterization. Coronary artery disease (CAD) severity was quantified in each subject via coronary angiography by calculating a CAD score. Circulating CXCL5 levels were measured from plasma, and both DNA genotyping and mRNA expression levels in peripheral blood mononuclear cells were quantified via microarray gene chips. We observed a negative association of CXCL5 levels with CAD at an odds ratio (OR) of 0.46 (95% CI, 0.27-0.75). Controlling for covariates, including sex, statin use, hypertension, hyperlipidemia, obesity, self-reported race, smoking, and diabetes, the OR was not significantly affected [OR, 0.54 (95% CI, 0.31-0.96)], consistent with a protective role for CXCL5 in coronary atherosclerosis. We also identified 18 genomic regions with expression quantitative trait loci of genes correlated with both CAD severity and circulating CXCL5 levels. Our clinical findings are consistent with the emerging link between chemokines and atherosclerosis and suggest new therapeutic targets for CAD.

SUBMITTER: Ravi S

PROVIDER: S-EPMC5718092 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical Evidence Supports a Protective Role for CXCL5 in Coronary Artery Disease.

Ravi Saranya S Schuck Robert N RN Hilliard Eleanor E Lee Craig R CR Dai Xuming X Lenhart Kaitlin K Willis Monte S MS Jensen Brian C BC Stouffer George A GA Patterson Cam C Schisler Jonathan C JC

The American journal of pathology 20171116 12

Our goal was to measure the association of CXCL5 and molecular phenotypes associated with coronary atherosclerosis severity in patients at least 65 years old. CXCL5 is classically defined as a proinflammatory chemokine, but its role in chronic inflammatory diseases, such as coronary atherosclerosis, is not well defined. We enrolled individuals who were at least 65 years old and undergoing diagnostic cardiac catheterization. Coronary artery disease (CAD) severity was quantified in each subject vi ...[more]

PMID: 29153655

Similar Datasets

Project description:To date there is no clear explanation as to how Chlamydia pneumoniae heat shock protein 60 (cHSP60) gets activated either through TLR-2/4, MAPKinase (p38/JNK/ERK), apoptotic/antiapoptotic, chemokines and inflammatory cytokines pathways leading to coronary artery disease (CAD). Hence to better understanding towards cHSP60 signaling in CAD patients, we performed experiments at RNA levels in cHSP60 positive and negative groups of CAD patients. For the determination of positivity for C. pneumoniae, Helicobacter pylori, Cytomegalovirus and Herpes Simplex Virus in atheromatous plaque multiplex Real Time PCR was performed. Monoplex Real Time PCR was also performed with 16S rRNA and HSP60 gene Chlamydia pneumoniae. Further study was performed only on cHSP60 positive (negative for H. pylori, CMV & HSV-1) and cHSP60 negative (also negative for H. pylori, CMV & HSV-1) CAD patients. 1. Patients Forty patients (28 males, 12 females) in age group (51Â±13 year) attending Department of Cardio Thoracic & Vascular Surgery, Safdarjung Hospital, New Delhi from September 2007 to April 2008 were enrolled in the study. These patients had manifestations of CAD and were undergoing open by-pass heart surgery. Prior written consent was obtained from each patient. The study received clearance from Ethical committee, Safdarjung hospital. Patients who had a recent acute coronary syndrome or transient ischemic attack were not included in our study. 2. Atheroma collection and handling Atheromatous tissue were collected in aseptic conditions and placed in 30 ml transport medium immediately upon resection. Three types of transport medium were used for tissue: viz. Dulbecco?s phosphate-buffered saline (PBS; Gibco Life Technologies, Paisley, Scotland) for DNA, RNA later (Ambion Inc., Woodward st. Austin, Texas, USA) for RNA and optimum cutting temperature compound (Sigma, St. Louis, MO, USA) for protein. 3. Atheroma DNA & RNA isolation and testing Total DNA was isolated for checking the positivity for C. pneumoniae from atheromatous plaques as described earlier [1]. Total RNA from the atheroma samples were isolated using RNeasy fibrous tissue mini kit (Qiagen Sciences, Maryland, USA) and the concentration was determined by a RNA dye-binding assay (Pico-Green, Molecular Probes, Eugene, OR). For cDNA synthesis, RETRO script (Ambion Inc., Woodward st. Austin, Texas, USA) was used as per manufacturer instructions. For detecting positivity for C. pneumoniae, Helicobacter pylori, Cytomegalovirus and Herpes Simplex Virus in atheromatous plaques, multiplex RT-PCR was performed [as describe in reference 1]. Monoplex RT PCR amplification primers and probes were custom designed by Applied Biosystems (Foster City, CA, USA). Briefly, sequences for the 16S rRNA and HSP60 gene of the organisms of interest were aligned and inspected for regions of conserved and variable sequences. 4. Microarray experiment Further study was performed only on cHSP60 positive (negative for H. pylori, CMV & HSV-1) and cHSP60 negative (also negative for H. pylori, CMV & HSV-1) CAD patients. cHSP60 positive samples represented the test samples and cHSP60 negative samples represented the control samples. 3 samples were analysed: samples 17 and 23 were biological replicates of test samples and also performed in duplicate as technical replicates, and sample 26 was a control sample and was also performed in duplicate as a technical replicate. Reference 1. Hem C Jha, Pragya Srivastava, Aabha Divya , Jagdish Prasad, Aruna Mittal. Prevalence of Chlamydophila pneumoniae is higher in aorta and coronary artery than in carotid artery of coronary artery disease patients. APMIS, 2009: 117 (12): 905-911.

Project description:Background-Coronary endarterectomy (CEA) has been introduced to allow revascularization in end-stage coronary artery disease (CAD). After CEA, the injured remnants of the vessel's media could result in fast neo intimal tissue ingrowth, which require an anti-proliferation agent (antiplatelet therapy (APT). We aimed to review outcomes of patients undergoing CEA within bypass surgery who received either single-APT (SAPT) or dual-APT (DAPT). Methods-We retrospectively evaluated 353 consecutive patients undergoing CEA within isolated coronary artery bypass grafting (CABG) in the period 01/2000-07/2019. After surgery, patients received either SAPT (n = 153), or DAPT (n = 200) for six months then lifelong SAPT. Endpoints included early, late survival, and freedom from major-adverse-cardiac and cerebrovascular events (MACCE), which were defined as incidence of stroke, myocardial infarction, need for coronary intervention (PCI or CABG) or death for any cause. Results-Patients' mean age was 67 ± 9.3 years; they were predominantly male 88.1%. Both DAPT- and SAPT-groups had the same extent of CAD (mean SYNTAX-Score-II: 34.1 ± 11.6 vs. 34.4 ± 17.2, p = 0.91). Postoperatively, no difference between DAPT- and SAPT-groups was reported in the incidence of low-cardiac-output syndrome (5% vs. 9.8%, p = 0.16), revision for bleeding (5% vs. 6.5% p = 0.64), 30-day mortality (4.5% vs. 5.2%, p = 0.8) or MACCE (7.5% vs. 11.8%, p = 0.19). Imaging follow-up reported significantly higher CEA and total grafts patency (90% vs. 81.5% and 95% vs. 81%, p = 0.017) in DAPT patients. Late outcomes within 97.4 ± 67.4 months show lower incidence of overall mortality (19 vs. 51%, p < 0.001) and MACCE (24.5 vs. 58.2%, p < 0.001) in the DAPT patients when compared with SAPT patients. Conclusions-Coronary endarterectomy allows revascularization in end-stage CAD when the myocardium is still viable. The use of dual APT after CEA for at least six months seems to improve mid-to-long-term patency rates and survival, and reduced the incidence of major adverse cardiac and cerebrovascular events.

Project description:Coronary artery disease (CAD) remains the leading cause of death worldwide with approximately 1 in 30 patients with stable CAD experiencing death or acute myocardial infarction each year. The presence and extent of resultant myocardial ischaemia has been shown to confer an increased risk of adverse outcomes. Whilst, optimal medical therapy (OMT) forms the cornerstone of the management of patients with stable CAD, a significant number of patients present with ischaemia refractory to OMT. Historically coronary angiography alone has been used to determine coronary lesion severity in both stable and acute settings. It is increasingly clear that this approach fails to accurately identify the haemodynamic significance of lesions; especially those that are visually "intermediate" in severity. Revascularisation based upon angiographic appearances alone may not reduce coronary events above OMT. Technological advances have enabled the measurement of physiological indices including the fractional flow reserve, the index of microcirculatory resistance and the coronary flow reserve. The integration of these parameters into the routine management of patients presenting to the cardiac catheterization laboratory with CAD represents a critical adjunctive tool in the optimal management of these patients by identifying patients that would most benefit from revascularisation and importantly also highlighting patients that would not gain benefit and therefore reducing the likelihood of adverse outcomes associated with coronary revascularisation. Furthermore, these techniques are applicable to a broad range of patients including those with left main stem disease, proximal coronary disease, diabetes mellitus, previous percutaneous coronary intervention and with previous coronary artery bypass grafting. This review will discuss current concepts relevant to coronary physiology assessment, its role in the management of both stable and acute patients and future applications.

Dataset Information

Clinical Evidence Supports a Protective Role for CXCL5 in Coronary Artery Disease.

Publications

Clinical Evidence Supports a Protective Role for CXCL5 in Coronary Artery Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets