Skip to main content
Top
Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease

Authors: Xiaomin Dang, Xiaoyan Qu, Weijia Wang, Chongbing Liao, Ying Li, Xiaojin Zhang, Dan Xu, Carolyn J. Baglole, Dong Shang, Ying Chang

Published in: Respiratory Research | Issue 1/2017

Login to get access

Abstract

Background

Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible chronic inflammatory disorder typified by increased recruitment of monocytes, lymphocytes and neutrophils. Because of this, as well as the convenience of peripheral blood nuclear cells (PBMCs) assessments, miRNA profiling of PBMCs has drawn increasing attention in recent years for various disease. Therefore, we analyzed miRNA and mRNA profiles to understand their regulatory network between COPD subjects versus smokers without airflow limitation.

Methods

miRNA and mRNA profiling of PBMCs from pooled 17 smokers and 14 COPD subjects was detected by high-throughput microarray. The expression of dysregulated miRNAs were validated by q-PCR. The miRNA targets in dysregulated mRNAs were predicted and the pathway enrichment was analyzed.

Results

miRNA microarray showed that 8 miRNAs were up-regulated and 3 miRNAs were down-regulated in COPD subjects compared with smokers; the upregulation of miR-24-3p, miR-93-5p, miR-320a and miR-320b and the downregulation of miR-1273 g-3p were then validated. Bioinformatic analysis of regulatory network between miRNA and mRNA showed that NOD and TLR were the most enriched pathways. miR-24-3p was predicted to regulate IL-18, IL-1β, TNF, CCL3 and CCL4 and miR-93-5p to regulate IκBα.

Conclusions

The expression of miRNA and mRNA were dysregulated in PBMCs of COPD patients compared with smokers without airflow limitation. The regulation network between the dysregulated miRNA and mRNA may provide potential therapeutic targets for COPD.
Literature
1.
go back to reference Pauwels RA, Rabe KF. Burden and clinical features of chronic obstructive pulmonary disease (COPD). Lancet. 2004;364:613–20.CrossRefPubMed Pauwels RA, Rabe KF. Burden and clinical features of chronic obstructive pulmonary disease (COPD). Lancet. 2004;364:613–20.CrossRefPubMed
2.
go back to reference Cosio MG, Majo J, Cosio MG. Inflammation of the airways and lung parenchyma in COPD: role of T cells. Chest. 2002;121:160S–5S.CrossRefPubMed Cosio MG, Majo J, Cosio MG. Inflammation of the airways and lung parenchyma in COPD: role of T cells. Chest. 2002;121:160S–5S.CrossRefPubMed
3.
go back to reference Stankiewicz W, Dabrowski MP, Chcialowski A, Plusa T. Cellular and cytokine immunoregulation in patients with chronic obstructive pulmonary disease and bronchial asthma. Mediators Inflamm. 2002;11:307–12.CrossRefPubMedPubMedCentral Stankiewicz W, Dabrowski MP, Chcialowski A, Plusa T. Cellular and cytokine immunoregulation in patients with chronic obstructive pulmonary disease and bronchial asthma. Mediators Inflamm. 2002;11:307–12.CrossRefPubMedPubMedCentral
4.
go back to reference Cosio MG, Saetta M, Agusti A. Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med. 2009;360:2445–54.CrossRefPubMed Cosio MG, Saetta M, Agusti A. Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med. 2009;360:2445–54.CrossRefPubMed
6.
go back to reference Faruq O, Vecchione A. microRNA: Diagnostic Perspective. Front Med (Lausanne). 2015;2:51. Faruq O, Vecchione A. microRNA: Diagnostic Perspective. Front Med (Lausanne). 2015;2:51.
7.
go back to reference Booton R, Lindsay MA. Emerging role of MicroRNAs and long noncoding RNAs in respiratory disease. Chest. 2014;146:193–204.CrossRefPubMed Booton R, Lindsay MA. Emerging role of MicroRNAs and long noncoding RNAs in respiratory disease. Chest. 2014;146:193–204.CrossRefPubMed
8.
go back to reference Mansoori B, Mohammadi A, Shirjang S, Baradaran B. Micro-RNAs: The new potential biomarkers in cancer diagnosis, prognosis and cancer therapy. Cell Mol Biol (Noisy-le-Grand). 2015;61:1–10. Mansoori B, Mohammadi A, Shirjang S, Baradaran B. Micro-RNAs: The new potential biomarkers in cancer diagnosis, prognosis and cancer therapy. Cell Mol Biol (Noisy-le-Grand). 2015;61:1–10.
9.
go back to reference Ezzie ME, Crawford M, Cho JH, Orellana R, Zhang S, Gelinas R, et al. Gene expression networks in COPD: microRNA and mRNA regulation. Thorax. 2012;67:122–31.CrossRefPubMed Ezzie ME, Crawford M, Cho JH, Orellana R, Zhang S, Gelinas R, et al. Gene expression networks in COPD: microRNA and mRNA regulation. Thorax. 2012;67:122–31.CrossRefPubMed
10.
go back to reference Van Pottelberge GR, Mestdagh P, Bracke KR, Thas O, van Durme YM, Joos GF, et al. MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183:898–906.CrossRefPubMed Van Pottelberge GR, Mestdagh P, Bracke KR, Thas O, van Durme YM, Joos GF, et al. MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183:898–906.CrossRefPubMed
11.
go back to reference Savarimuthu Francis SM, Davidson MR, Tan ME, Wright CM, Clarke BE, Duhig EE, et al. MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression. BMC Genomics. 2014;15:88.CrossRefPubMedPubMedCentral Savarimuthu Francis SM, Davidson MR, Tan ME, Wright CM, Clarke BE, Duhig EE, et al. MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression. BMC Genomics. 2014;15:88.CrossRefPubMedPubMedCentral
12.
go back to reference Sato T, Liu X, Nelson A, Nakanishi M, Kanaji N, Wang X, et al. Reduced miR-146a increases prostaglandin E(2)in chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med. 2010;182:1020–9.CrossRefPubMedPubMedCentral Sato T, Liu X, Nelson A, Nakanishi M, Kanaji N, Wang X, et al. Reduced miR-146a increases prostaglandin E(2)in chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med. 2010;182:1020–9.CrossRefPubMedPubMedCentral
13.
go back to reference Lewis A, Riddoch-Contreras J, Natanek SA, Donaldson A, Man WD, Moxham J, et al. Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax. 2012;67:26–34.CrossRefPubMed Lewis A, Riddoch-Contreras J, Natanek SA, Donaldson A, Man WD, Moxham J, et al. Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax. 2012;67:26–34.CrossRefPubMed
14.
go back to reference Ma J, Lin Y, Zhan M, Mann DL, Stass SA, Jiang F. Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer. Lab Invest. 2015;95:1197–206.CrossRefPubMedPubMedCentral Ma J, Lin Y, Zhan M, Mann DL, Stass SA, Jiang F. Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer. Lab Invest. 2015;95:1197–206.CrossRefPubMedPubMedCentral
15.
go back to reference Leidinger P, Keller A, Borries A, Huwer H, Rohling M, Huebers J, et al. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD. Lung Cancer. 2011;74:41–7.CrossRefPubMed Leidinger P, Keller A, Borries A, Huwer H, Rohling M, Huebers J, et al. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD. Lung Cancer. 2011;74:41–7.CrossRefPubMed
16.
go back to reference Ren RJ, Zhang YF, Dammer EB, Zhou Y, Wang LL, Liu XH, et al. Peripheral Blood MicroRNA Expression Profiles in Alzheimer's Disease: Screening, Validation, Association with Clinical Phenotype and Implications for Molecular Mechanism. Mol Neurobiol. 2016;53:5772–81. Ren RJ, Zhang YF, Dammer EB, Zhou Y, Wang LL, Liu XH, et al. Peripheral Blood MicroRNA Expression Profiles in Alzheimer's Disease: Screening, Validation, Association with Clinical Phenotype and Implications for Molecular Mechanism. Mol Neurobiol. 2016;53:5772–81.
17.
go back to reference Yang M, Ye L, Wang B, Gao J, Liu R, Hong J, et al. Decreased miR-146 expression in peripheral blood mononuclear cells is correlated with ongoing islet autoimmunity in type 1 diabetes patients 1miR-146. J Diabetes. 2015;7:158–65.CrossRefPubMed Yang M, Ye L, Wang B, Gao J, Liu R, Hong J, et al. Decreased miR-146 expression in peripheral blood mononuclear cells is correlated with ongoing islet autoimmunity in type 1 diabetes patients 1miR-146. J Diabetes. 2015;7:158–65.CrossRefPubMed
18.
go back to reference Liu D, Zhao H, Zhao S, Wang X. MicroRNA expression profiles of peripheral blood mononuclear cells in patients with systemic lupus erythematosus. Acta Histochem. 2014;116:891–7.CrossRefPubMed Liu D, Zhao H, Zhao S, Wang X. MicroRNA expression profiles of peripheral blood mononuclear cells in patients with systemic lupus erythematosus. Acta Histochem. 2014;116:891–7.CrossRefPubMed
19.
go back to reference Huang DW, Sherman BT, Tan Q, Collins JR, Alvord WG, Roayaei J, et al. The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol. 2007;8:R183.CrossRefPubMedPubMedCentral Huang DW, Sherman BT, Tan Q, Collins JR, Alvord WG, Roayaei J, et al. The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol. 2007;8:R183.CrossRefPubMedPubMedCentral
20.
go back to reference Xu W, Liu M, Peng X, Zhou P, Zhou J, Xu K, et al. miR-24-3p and miR-27a-3p promote cell proliferation in glioma cells via cooperative regulation of MXI1. Int J Oncol. 2013;42:757–66.PubMed Xu W, Liu M, Peng X, Zhou P, Zhou J, Xu K, et al. miR-24-3p and miR-27a-3p promote cell proliferation in glioma cells via cooperative regulation of MXI1. Int J Oncol. 2013;42:757–66.PubMed
21.
go back to reference Fukuda Y, Kawasaki H, Taira K. Exploration of human miRNA target genes in neuronal differentiation. Nucleic Acids Symp Ser (Oxf). 2005;49:341–2. Fukuda Y, Kawasaki H, Taira K. Exploration of human miRNA target genes in neuronal differentiation. Nucleic Acids Symp Ser (Oxf). 2005;49:341–2.
22.
go back to reference Qin W, Shi Y, Zhao B, Yao C, Jin L, Ma J, et al. miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PLoS One. 2010;5:e9429.CrossRefPubMedPubMedCentral Qin W, Shi Y, Zhao B, Yao C, Jin L, Ma J, et al. miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PLoS One. 2010;5:e9429.CrossRefPubMedPubMedCentral
23.
go back to reference Cheng AM, Byrom MW, Shelton J, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 2005;33:1290–7.CrossRefPubMedPubMedCentral Cheng AM, Byrom MW, Shelton J, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 2005;33:1290–7.CrossRefPubMedPubMedCentral
24.
go back to reference Brunner S, Herndler-Brandstetter D, Arnold CR, Wiegers GJ, Villunger A, Hackl M, et al. Upregulation of miR-24 is associated with a decreased DNA damage response upon etoposide treatment in highly differentiated CD8(+) T cells sensitizing them to apoptotic cell death. Aging Cell. 2012;11:579–87.CrossRefPubMedPubMedCentral Brunner S, Herndler-Brandstetter D, Arnold CR, Wiegers GJ, Villunger A, Hackl M, et al. Upregulation of miR-24 is associated with a decreased DNA damage response upon etoposide treatment in highly differentiated CD8(+) T cells sensitizing them to apoptotic cell death. Aging Cell. 2012;11:579–87.CrossRefPubMedPubMedCentral
25.
go back to reference Fordham JB, Naqvi AR, Nares S. miR-24 Regulates Macrophage Polarization and Plasticity. J Clin Cell Immunol. 2015;6:362. Fordham JB, Naqvi AR, Nares S. miR-24 Regulates Macrophage Polarization and Plasticity. J Clin Cell Immunol. 2015;6:362.
27.
go back to reference Droemann D, Goldmann T, Tiedje T, Zabel P, Dalhoff K, Schaaf B. Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients. Respir Res. 2005;6:68.CrossRefPubMedPubMedCentral Droemann D, Goldmann T, Tiedje T, Zabel P, Dalhoff K, Schaaf B. Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients. Respir Res. 2005;6:68.CrossRefPubMedPubMedCentral
28.
go back to reference Zhi F, Cao X, Xie X, Wang B, Dong W, Gu W, et al. Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia. PLoS One. 2013;8:e56718.CrossRefPubMedPubMedCentral Zhi F, Cao X, Xie X, Wang B, Dong W, Gu W, et al. Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia. PLoS One. 2013;8:e56718.CrossRefPubMedPubMedCentral
29.
go back to reference Ayaz L, Gorur A, Yaroglu HY, Ozcan C, Tamer L. Differential expression of microRNAs in plasma of patients with laryngeal squamous cell carcinoma: potential early-detection markers for laryngeal squamous cell carcinoma. J Cancer Res Clin Oncol. 2013;139:1499–506.CrossRefPubMed Ayaz L, Gorur A, Yaroglu HY, Ozcan C, Tamer L. Differential expression of microRNAs in plasma of patients with laryngeal squamous cell carcinoma: potential early-detection markers for laryngeal squamous cell carcinoma. J Cancer Res Clin Oncol. 2013;139:1499–506.CrossRefPubMed
30.
go back to reference Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-beta8. Oncogene. 2011;30:806–21.CrossRefPubMed Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-beta8. Oncogene. 2011;30:806–21.CrossRefPubMed
31.
32.
go back to reference Yeung ML, Yasunaga J, Bennasser Y, Dusetti N, Harris D, Ahmad N, et al. Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1. Cancer Res. 2008;68:8976–85.CrossRefPubMedPubMedCentral Yeung ML, Yasunaga J, Bennasser Y, Dusetti N, Harris D, Ahmad N, et al. Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1. Cancer Res. 2008;68:8976–85.CrossRefPubMedPubMedCentral
33.
go back to reference Sepramaniam S, Armugam A, Lim KY, Karolina DS, Swaminathan P, Tan JR, et al. MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. J Biol Chem. 2010;285:29223–30.CrossRefPubMedPubMedCentral Sepramaniam S, Armugam A, Lim KY, Karolina DS, Swaminathan P, Tan JR, et al. MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. J Biol Chem. 2010;285:29223–30.CrossRefPubMedPubMedCentral
34.
go back to reference Wang H, Peng W, Ouyang X, Li W, Dai Y. Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus. Transl Res. 2012;160:198–206.CrossRefPubMed Wang H, Peng W, Ouyang X, Li W, Dai Y. Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus. Transl Res. 2012;160:198–206.CrossRefPubMed
35.
go back to reference Sanfiorenzo C, Ilie MI, Belaid A, Barlesi F, Mouroux J, Marquette CH, et al. Two panels of plasma microRNAs as non-invasive biomarkers for prediction of recurrence in resectable NSCLC. PLoS One. 2013;8:e54596.CrossRefPubMedPubMedCentral Sanfiorenzo C, Ilie MI, Belaid A, Barlesi F, Mouroux J, Marquette CH, et al. Two panels of plasma microRNAs as non-invasive biomarkers for prediction of recurrence in resectable NSCLC. PLoS One. 2013;8:e54596.CrossRefPubMedPubMedCentral
36.
go back to reference Guo J, Sang Y, Yin T, Wang B, Yang W, Li X, et al. miR-1273g-3p Participates in Acute Glucose Fluctuations Induced Autophagy, Dysfunction And Proliferation Attenuation in Human Umbilical Vein Endothelial Cells. Am J Physiol Endocrinol Metab. 2016;10:E734–43. doi:10.1152/ajpendo.00444.2015. Guo J, Sang Y, Yin T, Wang B, Yang W, Li X, et al. miR-1273g-3p Participates in Acute Glucose Fluctuations Induced Autophagy, Dysfunction And Proliferation Attenuation in Human Umbilical Vein Endothelial Cells. Am J Physiol Endocrinol Metab. 2016;10:E734–43. doi:10.​1152/​ajpendo.​00444.​2015.
37.
go back to reference Rachagani S, Macha MA, Menning MS, Dey P, Pai P, Smith LM, et al. Changes in microRNA (miRNA) expression during pancreatic cancer development and progression in a genetically engineered KrasG12D;Pdx1-Cre mouse (KC) model. Oncotarget. 2015;6:40295–309.PubMedPubMedCentral Rachagani S, Macha MA, Menning MS, Dey P, Pai P, Smith LM, et al. Changes in microRNA (miRNA) expression during pancreatic cancer development and progression in a genetically engineered KrasG12D;Pdx1-Cre mouse (KC) model. Oncotarget. 2015;6:40295–309.PubMedPubMedCentral
38.
go back to reference Szulakowski P, Crowther AJ, Jimenez LA, Donaldson K, Mayer R, Leonard TB, et al. The effect of smoking on the transcriptional regulation of lung inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;174:41–50.CrossRefPubMed Szulakowski P, Crowther AJ, Jimenez LA, Donaldson K, Mayer R, Leonard TB, et al. The effect of smoking on the transcriptional regulation of lung inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;174:41–50.CrossRefPubMed
39.
go back to reference de Boer WI. Perspectives for cytokine antagonist therapy in COPD. Drug Discov Today. 2005;10:93–106.CrossRefPubMed de Boer WI. Perspectives for cytokine antagonist therapy in COPD. Drug Discov Today. 2005;10:93–106.CrossRefPubMed
40.
go back to reference Meuronen A, Majuri ML, Alenius H, Mantyla T, Wolff H, Piirila P, et al. Decreased cytokine and chemokine mRNA expression in bronchoalveolar lavage in asymptomatic smoking subjects. Respiration. 2008;75:450–8.CrossRefPubMed Meuronen A, Majuri ML, Alenius H, Mantyla T, Wolff H, Piirila P, et al. Decreased cytokine and chemokine mRNA expression in bronchoalveolar lavage in asymptomatic smoking subjects. Respiration. 2008;75:450–8.CrossRefPubMed
41.
go back to reference Baldwin Jr AS. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–83.CrossRefPubMed Baldwin Jr AS. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–83.CrossRefPubMed
42.
go back to reference Barkett M, Gilmore TD. Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene. 1999;18:6910–24.CrossRefPubMed Barkett M, Gilmore TD. Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene. 1999;18:6910–24.CrossRefPubMed
43.
go back to reference Hodge S, Hodge G, Holmes M, Reynolds PN. Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation. Eur Respir J. 2005;25:447–54.CrossRefPubMed Hodge S, Hodge G, Holmes M, Reynolds PN. Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation. Eur Respir J. 2005;25:447–54.CrossRefPubMed
Metadata
Title
Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease
Authors
Xiaomin Dang
Xiaoyan Qu
Weijia Wang
Chongbing Liao
Ying Li
Xiaojin Zhang
Dan Xu
Carolyn J. Baglole
Dong Shang
Ying Chang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-016-0486-5

Other articles of this Issue 1/2017

Respiratory Research 1/2017 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.