27th European Cardiology Conference October 22-24, 2018 Rome, Italy

Biography:

Chiara Mozzini is an  Adjunct Professor in the section of Internal Medicine at University of Verona, Italy. Graduated from University of Brescia and Certified in 2012 with Specialist in Internal Medicine from University of Verona ,Italy. Board. With PhD certification in Clinical and experimental Medical Sciences, 2016. Research Fields: Atherosclerosis;- Cardiovascular Diseases; Coronary Artery Disease;- Diabetes;- Oxidative Stress;- Endoplasmic Reticulum Stress;- Ultrasound (Cardiac-Abdominal- Vascular).

Abstract:

To summarize the understanding of the interrelated roles of endoplasmic reticulum (ER) stress, oxidative stress and inflammation in cardiovascular diseases.  Insults interfering with ER function lead to the accumulation of unfolded and misfolded proteins in the ER. An excess of proteins folding in the ER is known as ER stress. This condition initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signalling is induced. Moreover, the role of the protective nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE) and the activation of the pro-inflammatory nuclear factor-kappa B (NF-kB) are analysed. Current literature data are presented, focusing on three topics of related pathologies: atherosclerotic plaque, coronary artery disease and diabetes. Moreover, current evidence suggests the likelihood of a link between venous thromboembolism (VTE) and atherosclerosis, although they have been traditionally considered as different pathological identities. The contribution of neutrophils to human atherogenesis has been underestimated, if compared to their contribution established in VTE. This is due to the major importance attributed to macrophages in the plaque destabilization. Nevertheless, recently, the role of neutrophils in atherogenesis deserves increasing attention. In particular, neutrophil extracellular traps (NETs) are net-like chromatin fibres which are released from dying neutrophils. The death of neutrophils with NETs formation is called NETosis. During activation, neutrophils produce Reactive Oxygen Species (ROS), through the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The main function of NETs is trapping and killing pathogens. However, NETs formation has been observed in various chronic inflammatory diseases, autoimmune diseases, vasculitis, lung diseases, cancer and VTE. Recent studies suggest that NETs formation could contribute also to atherosclerosis progression. New data report the presence of NETs in the luminal portion of human atherosclerotic vessels and coronary specimens obtained from patients after acute myocardial infarction. Programmed death mechanisms in atherosclerosis such as apoptosis, efferocytosis and also NETosis, share common features and triggers. If defective, they can lead the cells to  a switch from programmed death to necrosis, resulting in the release of pro-atherogenic factors, accumulation of cell debris and progression of the disease. This talk aims to analyse the emerging role of neutrophils focusing on NETosis and oxidative stress burden in orchestrating common mechanisms in atherosclerosis and thrombosis.

Biography:

Takeo Tedoriya has completed his PhD at the age of 28 years from Kanazawa University and trained cardiac surgery at German Heart Institute Berlin to get German board of cardiac surgery, thereafter moved to St.Vincent Hospital Sydney as a temporary consultant for heart-lung transplantation unit, after working at Kanazawa University Medical Center. He had been the professor and director of Showa University for 10 years, followed by the director of Ageo Central General Hospital, Cardiovascular Center. He has published more than 45 papers in reputed journals and has been serving as a reviewer for several journals.

Abstract:

Aortic valve reconstruction with three same-sized autologous pericardial leaflets has been performed for patients with narrow aortic roots or contraindication for valve-prostheses. Since this procedure requires precise information of the aortic root including configuration of Valsalva sinus, we assessed physiologic-anatomical condition of the aortic root by Virtual Reality (VR) Image in order to accomplish this technique with a reproducible fashion.  VR Imaging; Enrolled patients underwent enhanced ECG-triggered cardiac CT. Axial images using a 264-row CT with slice thickness of 0.625mm were obtained during mid-to-end diastole. Subtracted volume rendering data of the aortic root were converted to stereolithography (STL) file in Visalius3D, a novel 3D workstation.  Preoperatively the aortic root was assessed in order to decide neo-commissure and offsetting of deviated nadir in cases of unbalanced aortic root, like type 0 bicuspid valve. Basic surgical technique was; 1) same-sized three pieces of leaflets from autologous pericardium were tailored to original templates referred by STJ diameter, 2) the new commissures and nadirs were confirmed based on VR image (in case the non-coronary nadir deviated toward the left ventricle, a crescent form Valsalva plication were required), 3) three leaflets were sutured on the cusp-sutureline, 4) commissure coaptation stitches were placed between each leaflet to prevent from minor leakage and coronary orifices obstruction. Postoperative echocardiography revealed nicely opening of new-leaflet with no AR. VR image analysis had notably provides valuable information for understanding of precise anatomy of the aortic root.

Biography:

He started his career as a resident at the University Hospital in Giessen in 1978. In 1990 he became a full professor for cardiovascular surgery at the University in Bonn and vice chairman of the respective department. In 1989 and 1990 he spent two semesters at the Carolinas Heart Institute in Charlotte/NC as a research and clinical fellow. Since 1994,He is working at the University Hospital in Marburg as a full professor for cardiovascular surgery and director of the department. Between 2001 and 2011 he also held the position of the vice medical director and since 2006 the medical director of the University Hospital in Marburg. The main specialties within cardiovascular surgery are laser- and arrhythmia surgery, endovascular procedures including TAVI´s and endovascular reconstructions of the aortic arch and reconstructive surgery of the coronaries. As the chairman of the board of "Medical Network Hessen" he is an official representative of the State of Hessen in the field of clinical medicine and medical education.

Abstract:

While ventricular fibrillation is often induced by acute ischemia or the immediate sequelae of  it, ventricular tachycardia are mostly due to a pathological substrate such as even small scars or inflammatory infiltrates. As a consequence, sole revascularization does influence ischemia induced arrhythmias while most VTs remain unchanged. In case of necessary cardiac surgery, especially for myocardial revascularization, an intraoperative mapping and laser-ablation of the identified foci is recommended. If larger scars or even aneurysms are present, an endocardial and epicardial ablation is performed and has demonstrated its high efficacy with a successrate of more than 90%. In case of only small scars or infiltrates, we refrain from opening the ventricle and only perform an epicardial mapping and deep ablation, which is even curative in more than half oft he cases without further need of an ICD implantation, as demonstrated in a study with > 30 patients. As the whole procedure is performed on the beating heart, it does not add to ischemic time and does not increase the risk significantly.Laser-VT-ablation is an effective, less invasive, curative therapy for patients with an indication for open heart surgery, especially coronary revascularization, and with documented VTs.

Biography:

Tamara Feygin is an Associate Professor of Clinical Radiology at the University of Pennsylvania, Perelman School of Medicine, and a pediatric neuroradiologist at The Children’s Hospital of Philadelphia. Her primary interests are fetal and neonatal imaging. Dr. Feygin led the development and implementation of magnetic resonance “fluoroscopy” in clinical practice for assessment of dynamic processes in fetuses. Dr. Feygin is a dedicated educator and mentor of medical students, radiology residents, and radiology and neuroradiology fellows.  Dr. Feygin is a co-author of books, chapters and scientific peer-reviewed papers. She has been invited to present her work nationally and internationally. She is a member of the European Society of Neuroradiology, the Radiological Society of North America, the Society for Pediatric Radiology, and a senior member of the American Society of Neuroradiology.

Abstract:

A variety of congenital heart diseases (CHD) may be diagnosed prenatally. Traditionally, the fetal heart was primarily assessed by fetal echography. However, fetal MRI has been proven as a helpful imaging tool in detection of cardio-vascular anomalies in utero. Numerous conditions, including aorta coarctation, hypoplastic left heart syndrome, tetralogy of Fallout, cardiac aneurysms, pericardial/cardiac tumors may be successfully detected on MR imaging. In addition, presence of other coexisting anomalies outside of the cardio-vascular system may be revealed. Some cardio-vascular anomalies may be more than an isolated problem and could be a part of an underlying systemic/genetic condition. Even in the absence of genetic abnormalities, infants with CHD are at increased risk of brain lesions (15-45%) or neurodevelopmental delay.   The demonstration of a full spectrum of fetal anomalies provides extremely valuable information to clinicians and parents-to be.   Fetal MR may be a feasible addition for timely and precise diagnosis of cardiac disease and associated anomalies. Prenatal imaging therefore helps to predict pregnancy outcome, and prepares couples for the birth of a child with an abnormality.  The obtained information may also assist in thorough screening of fetal patients for eligibility for fetal treatment. It may help to prognosticate to some degree important issues of patient’s developmental outcome and quality of life.

Biography:

Jochen Senges is the Director of the Institute of Herzinfarktforschung Ludwigshafen. He completed his Medical School at University of Heidelberg, Berlin and Frankfurt 1961-1966; Medical Diploma at University of Heidelberg in 1966; Board certification in Internal Medicine in 1974. He was a Senior Staff Physician in Department of Cardiology, University of Heidelberg. He completed his PhD in Medicine with a neurophysiologic dissertation at University of Heidelberg in 1967 and; was a Research Fellow at Stanford University, California, USA in 1969. His main research topic is Cardiac Arrhythmias. He was an Associate Professor of the Medical Faculty, University of Heidelberg in 1981.

Abstract:

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and affects mainly older people. Poor diagnosis of AF: Large registries (Gloria-AF) have clearly shown that about 2thirds of patients in Western Europe with newly diagnosis nonvalvular AF are detected asymptomatic/minimally symptomatic. The rate of previous stroke in these patients is more than twice as high as in symptomatic patients, despite no difference in CHA2DS2-VASc-Score. This may be explained by a longer but subclinical and therefore undiagnosed AF history. Poor medical adherence: poor medication adherence is the second most important factor underlying strokes in patients with atrial fibrillation. Various major studies have demonstrated that less than half of AF-patients are treated with guideline antithrombotic medication. Mass media campaign: these results underline the importance for both: public programs to detect non-valvular AF in the older population but also public education programs that should focus on patients poor understanding of the importance for sustained antithrombotic medication adherence to prevent stroke. The ARENA study includes a longstanding mass media campaign over one year to improve diagnosis and medical adherence in atrial fibrillation. Actually over 10.000 AF-patients are documented and first results will be presented at this meeting. 

Biography:

Ingrid Dumitriu is a Reader (Associate Professor) in Cardiovascular Immunology at St. George’s, University of London, London UK. She leads the Cardiovascular Immunology research group and has an MD degree and a PhD in Immunology. Her research focuses on the role of inflammation and immune cells in atherosclerosis and other cardiovascular diseases. Dr Dumitriu is a nucleus member of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Biology. She is also a member of the ESC, European Atherosclerosis Society, British Society for Immunology, and ESC Working Group on Peripheral Circulation.

Abstract:

The precise role of inflammation in the development and perpetuation of atrial fibrillation (AF) is yet to be fully uncovered. T and B lymphocytes, the main cellular effectors of adaptive immunity, have pivotal roles in orchestrating inflammation. Different subsets of lymphocytes either promote or prevent inflammation. We are investigating a unique subset of lymphocytes, the CD4+CD28null T cells that expand in patients with chronic inflammation. These cells secrete high levels of pro-inflammatory cytokines tumour necrosis factor-α (TNF-α) and interferon-g (IFN-g). The response of CD4+CD28null T cells is normally maintained under control by regulatory T cells (Treg), a specialised subset of T lymphocytes with suppressive function that maintain immune homeostasis and prevent pathogenic immune responses. The role of CD4+CD28null and Treg cells has not been investigated in AF. We found that CD4+CD28null T lymphocytes were significantly increased in the circulation of AF patients compared to controls (p<0.0001). In addition, AF patients had a marked reduction (p=0.0001) in Treg cells. The ratio of CD4+CD28null T lymphocytes to Tregs was significantly increased. In contrast, no alterations were identified in circulating B cell subsets. Levels of hsCRP, TNF-α and IFN-g did not correlate with CD4+CD28null T cell and Treg frequency. Instead, we demonstrate that the expansion of CD4+CD28null T cells is caused by defects in apoptosis pathways and increased activation and proliferation in response to homeostatic cytokines. These novel results suggest an imbalance in the mechanisms that maintain homeostasis in the immune response, which may promote inflammation in patients with AF.

Biography:

Heinz-Peter Schultheiss, Professor of Internal Medicine and Cardiology, is CEO of Institute for cardiac diagnostic and therapy (IKDT) Berlin, Germany since 2003. He was the chairman of the Working group “Inflammatory heart muscle diseases“ of the German Society of Cardiology, Chairman of the “Working Group on Myocardial and Pericardial Disease“ of the European Society of Cardiology, Member of the "Council on Cardiomyopathies“ of the International Society of Cardiology, Chairman of the Medical Society Berlin, Member of German Society for Internal Medicine, Member of European Society of Cardiology.

Abstract:

Cardiomyocytes can be destroyed by direct virus damage, the antiviral immune response, or a truly autoimmune injury. Beside an optimal heart failure therapy, the mainstay of treatment for myocarditis and inflammatory cardiomyopathy (CMi) is the biopsy-proven specific immunomodulatory treatment regarding the underlying pathophysiological mechanisms. Chronic viral infections of the heart (mainly Parvovirus B19, Human-Herpes virus (HHV) 6, Coxsackie-adeno virus, Ebstein-Barr virus, Cytomegalie virus, and Hepatitis virus) are considered one antecedent event leading to progressive dysfunction of the myocardium, often with an impaired prognosis due to a virus- or immune-mediated myocardial injury. The effectiveness of anti-viral-therapy has been proven in recent studies, showing that enterovirus/ adenovirus – positive patients benefit from anti-viral therapy with interferon beta-1b, whereas in patients suffering from parvovirus B19 infection no established therapy exists. However, the nucleoside analogues Telbivudine seems to be a promising drug in patients with proof of active viral replication. Follow-up studies revealed an association with HHV6 and the clinical course of myocarditis and CMi. HHV-6 is able to integrate its genomes into telomeres of human chromosomes. We recently demonstrated that antiviral therapy with Ganciclovir can diminish HHV-6 replication as well as cardiac symptoms of these patients. Myocardial inflammatory processes due to autoimmunity warrant immunosuppressive treatment in order to prevent immune-mediated myocardial injury. Immunosuppression (treatment with prednisone and azathioprine for 6 months) demands biopsy-based exclusion of virus since virus-positive patients do not improve or even deteriorate under anti-inflammatory treatment, while virus-negative patients with post-infectious, auto-immune inflammatory process respond well in clinical trials, and - after termination - long lasting LVEF improvement has been documented.

Biography:

Peter Ott obtained his medical degree from the University of Heidelberg, Germany. After Internal Medicine residency (Tucson, Arizona), he pursued specialty training in cardiology (Denver, Colorado) and cardiac electrophysiology (Salt Lake City, Utah).  Since 1999 he is a leading member of the cardiac electrophysiology section at the Sarver Heart Center, University of Arizona. He has published in numerous reputed, peer-reviewed journals.

Abstract:

Advances in pacemaker technology and expanding use of cardiac rhythm monitoring devices have resulted in detection of thus far undiagnosed atrial fibrillation (AF). These device-detected episodes, typically brief in duration (minutes to hours) and mostly asymptomatic, are often referred to as “subclinical atrial fibrillation” (SCAF).  While clinical atrial fibrillation, typically diagnosed by routine EKG/48 hour Holter recording is a well-known risk factor for stroke, the therapeutic implications for device detected SCAF remain unknown.

Three recent long-term studies investigated the incidence of SCAF by means of implanted loop recorder devices in a total of 950 patients deemed at risk for AF based on age (>65-70 years) plus additional risk factors. The incidence of SCAF (defined as > 6 minutes in duration) ranged from 22-34% at 18 months follow up. Most episodes were asymptomatic and brief in duration (<30 minutes).  Episode duration > 24 hours comprised only 10% of all SCAF episodes.

Several studies in patients undergoing pacemaker or ICD implantation investigated the prevalence and clinical implications of device detected SCAF.  The patient populations (some trials enrolled patients with a prior history of stroke and AF) and definitions of SCAF varied (ranging from > 5 minutes to > 24 hours), the incidence of SCAF ranged from approximately 20-50% at 12-18 months follow up. Overall there were no important differences in clinical risk factors such as age, CHADS score, comorbidities, etc, between patients with and without SCAF. Compared to patients without SCAF those with SCAF had a higher incidence of subsequent diagnosis of clinical AF (HR 5-6) and an increase in rates of thrombo-embolic (TE) complications (HR 2-2.5). The absolute number of stroke events was small, and none of these trials controlled for use of anticoagulation or antiplatelet therapy.  While the relative risk of TE events was increased in patients with SCAF the absolute risk varied 1.0–2.5%/year. The stroke risk was highest in patients with increased CHADS stroke risk score and/or prolonged SCAF episode duration. A recent analysis in 2,580 pacemaker recipients > 65 years of age and no prior history of AF showed increased stroke rates only in patients with SCAF > 24 hrs duration. In this large trial the overall incidence of SCAF was approx. 20% at 1-2 year follow up, and only 25% of SCAF episodes were > 24 hours in duration.

Biography:

Chiara Mozzini is an  Adjunct Professor in the section of Internal Medicine at University of Verona, Italy. Graduated from University of Brescia and Certified in 2012 with Specialist in Internal Medicine from University of Verona ,Italy. Board. With PhD certification in Clinical and experimental Medical Sciences, 2016. Research Fields: Atherosclerosis;- Cardiovascular Diseases; Coronary Artery Disease;- Diabetes;- Oxidative Stress;- Endoplasmic Reticulum Stress;- Ultrasound (Cardiac-Abdominal- Vascular).

Abstract:

This presentation is intended primarily to summarize the understanding of the interrelated   roles of endoplasmic reticulum (ER) stress, oxidative stress and inflammation in cardiovascular diseases.

Insults interfering with ER function lead to the accumulation of unfolded and misfolded proteins in the ER. An excess of proteins folding in the ER is known as ER stress. This condition initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signalling is induced. Moreover, the role of the protective nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE) and the activation of the pro-inflammatory nuclear factor-kappa B (NF-kB) are analysed. Oxidative stress, inflammation and ER stress are closely entwined phenomena. They are involved in the pathogenesis of different cardiovascular diseases. Current literature data are presented, focusing on three topics of related pathologies: atherosclerotic plaque, coronary artery disease and diabetes.This presentation provides a basic platform for study and application to several other conditions in which oxidative stress, ER stress and inflammation are key features. Future studies in this area may identify the most promising molecules to be investigated as common targets for cardiovascular disease.

Biography:

Ryan Buendia has completed his medical school in De la Salle University in the Philippines. He finished his Adult Cardiology training and Interventional Cardiology training in St. Luke’s Medical Center Global City. He further trained in Cardiovascular Institute, Tokyo, Japan and  in Chang Gung Memorial Hospital, Kaohsiung,  Taiwan for peripheral interventions. He also had training in Extracorporeal Membrane Oxygenator (ECMO) management in La Pitie’-Salpetriere University hospital in Paris, France. He is currently an assistent training officer in Interventional Cardiology n his institution. He is a member of the STEMI Committee of the Philippine Society of Cardiac Catheterizations and Interventions.

Abstract:

Acute Coronary Syndromes, particularly ST segment elevation Myocardial Infarction (ACS-STEMI) is highest cause of morbidity and mortality among cardiovascular disease both in developed countries in the west and also in Asia and the Pacific region. Primary angioplastyis the gold standard of therapeutic care and has proven to decrease in-hospital mortality, 30 day mortality, rehospitalizations, heart failure incidence, life thretening arrythmias and improve quality if life among patients. The days of thrombolytic therapy are gone and primary angioplasty is the primary tool to treat such patients in our population. It is a quick, minimally invasive procedure that would save as much myocardium as possible during ACS-STEMI and ESC/AHA recommendations encourage to get patients into the less than 90 minute door-to-open artery time. Established systems and centers even created recommendations to push door-toopen artery time to less than 60 minutes.

This is very ideal in the setting of developed countries with adequate access to cardiac catheterization labs and efficient ambulance service, not to mention adequate health insurance coverage. Countries in the Southeast Asian regions such as Singapore, Thailand, Malaysia and recently Vietnam have been able to establish their nationwide, government supported STEMI systems. The ASEAN population has trend towards increasing incidence of coroanry artery disease similar to the Western and European population. The hub-and-spoke model is an efficient way to channel STEMI patients directly to PCI-capable hospitals and would give such patients proper treatment in collaboration to thrombolytic therapy in far, non-PCI hospitals. The Philippines, with a population of 102 million people, the country being an archipelago or group of islands, as a nation has a very challenging geographical, not to mention economical demographics in terms of formulating a STEMI program bioth in metropolitan and urban/provincial areas. These factors, together with a lack of health insurance coverage and government support in a developing country such as the Philippines had created a very big challenge to health care providers in terms of delivering both efficient thrombolytic therapy and systemised nationwide STEMI program. The author and a group of cardiac interventionists in the country realizing these needs, spearheaded programs within their respective institutions to create STEMI programs and be identified to be “hubs” to “spokes” around Metro Manila (the country’s capital) and a dediated program in the province of Batangas (south of Manila) in the urban setting.  The author’s own institution, St. Luke’s Medical Center Global City in Metro Manila, initiated a systemised STEMI program and is the first to launch an efficient 24/7 PCI capability. The system established, with the commitment of 21 rotating interventional cardiologists were able to decrease the door-to-open artery/door-to-balloon time from 156 minutes to 86 minutes in a period of 1 year (2010-2014 (without STEMI system and 2014-2015 (with STEMI system). This commitment and focus on providing efficient primary PCI services 24/7 inspired other PCI capable hospitals in Metro Manila to create their own system as well. 

Biography:

Maliheh Nazari-Jahantigh received her bachelor and master degrees in the field of cellular and molecular biology from Iran and selected as an outstanding student in the country during her master studies. She completed her PhD in 2013 from RWTH Aachen University in the field of biology and then started her postdoctoral studies in Ludwig Maximillian University Munich. Currently she is a junior group leader at institute for cardiovascular disease (IPEK) in LMU. She has been studying the role of microRNAs during atherosclerosis since 2009 and has published several papers in reputed journals in this field.

Abstract:

Atherosclerosis is the main cause of cardiovascular disease that are number one killer worldwide. Macrophage dysfunction contributes to the progression of atherosclerosis and microRNAs, negative regulators of gene expression, mediate macrophage function upon activation. miR-147 is upregulated in inflammatory macrophages as well as murine and human atherosclerotic plaques, while it is downregulated in peripheral monocytes from patients with coronary artery disease. However, the role of macrophage-miR-147 in atherosclerosis is yet unknown. To study that, we generated a mouse line with a deletion of the miR-147 gene in myeloid cell line, Apoe^-/-LysMcreMir147^flox/flox (M-Mir147^-/-), and together with Apoe^-/-LysMcreMir147^+/+ (M-Mir147^+/+) mice fed them a high cholesterol diet (HCD) for 12 wks. miR-147 deficiency in macrophages increased atherosclerosis in M-Mir147^-/- versus M-Mir147^+/+ mice. The Increased lesion size was associated with enlarged necrotic core area, increased lesional macrophage content, increased cell death, and impaired clearance of apoptotic cells by macrophages.  The effects of miR-147 deletion on proteome of inflammatory macrophages was studied by mass spectrometry in vitro and suggests that energy metabolism and Akt/mTOR signaling are the main targets of miR-147 in inflammatory macrophages. MiR-147 interactome was studied in inflammatory macrophages from M(tAgo2)-Mir147^-/- and M(tAgo2)-Mir147^+/+ mice, which express a tagged Ago2 gene following Cre recombinase activity, using an in vitro tAgo2 immunoprecipitation assay followed by RNA sequencing. Integrated analysis of interactome and proteome data suggested Tomm6, Pdk3, and Pim1 as potential targets of miR-147 in inflammatory macrophages. Our results indicate that macrophage-miR-147 plays a protective role against atherosclerosis probably by improving macrophage function under inflammatory condition.

Biography:

Chiara Mozzini is an  Adjunct Professor in the section of Internal Medicine at University of Verona, Italy. Graduated from University of Brescia and Certified in 2012 with Specialist in Internal Medicine from University of Verona ,Italy. Board. With PhD certification in Clinical and experimental Medical Sciences, 2016. Research Fields: Atherosclerosis;- Cardiovascular Diseases; Coronary Artery Disease;- Diabetes;- Oxidative Stress;- Endoplasmic Reticulum Stress;- Ultrasound (Cardiac-Abdominal- Vascular).

Abstract:

To summarize the understanding of the interrelated roles of endoplasmic reticulum (ER) stress, oxidative stress and inflammation in cardiovascular diseases.  Insults interfering with ER function lead to the accumulation of unfolded and misfolded proteins in the ER. An excess of proteins folding in the ER is known as ER stress. This condition initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signalling is induced. Moreover, the role of the protective nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE) and the activation of the pro-inflammatory nuclear factor-kappa B (NF-kB) are analysed. Current literature data are presented, focusing on three topics of related pathologies: atherosclerotic plaque, coronary artery disease and diabetes. Moreover, current evidence suggests the likelihood of a link between venous thromboembolism (VTE) and atherosclerosis, although they have been traditionally considered as different pathological identities. The contribution of neutrophils to human atherogenesis has been underestimated, if compared to their contribution established in VTE. This is due to the major importance attributed to macrophages in the plaque destabilization. Nevertheless, recently, the role of neutrophils in atherogenesis deserves increasing attention. In particular, neutrophil extracellular traps (NETs) are net-like chromatin fibres which are released from dying neutrophils. The death of neutrophils with NETs formation is called NETosis. During activation, neutrophils produce Reactive Oxygen Species (ROS), through the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The main function of NETs is trapping and killing pathogens. However, NETs formation has been observed in various chronic inflammatory diseases, autoimmune diseases, vasculitis, lung diseases, cancer and VTE. Recent studies suggest that NETs formation could contribute also to atherosclerosis progression. New data report the presence of NETs in the luminal portion of human atherosclerotic vessels and coronary specimens obtained from patients after acute myocardial infarction. Programmed death mechanisms in atherosclerosis such as apoptosis, efferocytosis and also NETosis, share common features and triggers. If defective, they can lead the cells to  a switch from programmed death to necrosis, resulting in the release of pro-atherogenic factors, accumulation of cell debris and progression of the disease. This talk aims to analyse the emerging role of neutrophils focusing on NETosis and oxidative stress burden in orchestrating common mechanisms in atherosclerosis and thrombosis.