Pharmacology of Thrombosis and Atherosclerosis
|Marina Camera (Associate Professor)|
Luigi Sironi (Associate Professor)
|Laura Castiglioni (Laboratory technician)|
Paolo Gelosa (Contract worker)
Donato Moschetta (PhD student)
Joanna Rzemieniec (Postdoctoral fellow)
Majeda Muluhie (PhD student)
Benedetta Mercuriali (Scholarship holder)
The unit's research activity is divided into two main areas:
- The study of cellular and molecular mechanisms involved in the development of cardio- and cerebrovascular pathologies, and the evaluation of innovative pharmacological approaches that could be used for the prevention and treatment of these diseases by focusing mainly on the repositioning of drugs that are already known and used in the clinical field.
- The study of cellular and molecular mechanisms involved in the thrombotic complications of cardiovascular pathologies and their pharmacological modulation with a particular attention to the effect of cardiovascular risk factors on platelet activity.
DESCRIPTION OF RESEARCH TOPICS
1. The research carried out is aimed at characterizing the mechanisms underlying the development and progression of cerebral, cardiac and renal ischemia as well as the pathological conditions that set in after ischemic insult and lead to the maladaptive tissue remodeling process. Particular attention is paid to the evolution of ischemic damage, the involvement of inflammatory processes and the alterations of mitochondrial dynamics. These studies are aimed at identifying both molecular and cellular targets for new and effective therapies that are involved in the treatment and prevention of vascular diseases which occur as a result of ischemic insult.
To achieve this, the unit makes use of the expertise acquired by its members in the use of in vivo imaging techniques, in particular magnetic resonance imaging (MRI) and high-definition ultrasound. These non-invasive techniques make it possible to visualize and follow in-vivo the evolution of a wide range of pathologies, such as cardiac hypertrophy and heart failure, renal diseases and cerebral and cardiac ischemia. To this end, a Bruker Avance II scanner operating at 4.7 T is used for MRI analysis, and a Vevo 2100 platform is used to perform echocardiographic studies on rodents, further extending the unit's capacity to perform longitudinal in vivo studies in a totally non-invasive manner.
2. The second line of research, aimed at the evaluation and pharmacological modulation of the cellular and molecular mechanisms involved in thrombotic complications of cardiovascular diseases, is divided into the following projects:
- Characterisation of new pathways of platelet activation and identification of the pathophysiological mechanisms involved.
- Pharmacological modulation of thrombotic complications in cardiovascular diseases. In this context, a major line of research aims to evaluate the modulation of Tissue Factor expression by drugs such as statins, ACE inhibitors, antiplatelet agents, etc., in order to reduce the risk of thrombosis. Tissue Factor is indeed a key protein in the activation of blood coagulation and directly responsible, together with platelets, for the thrombotic complications of coronary syndrome, both "primary" and "secondary" to interventional cardiology procedures (coronary and carotid stents) and cardiac surgery (aortocoronary bypass, aortic aneurysms).
- Molecular mechanisms responsible for interindividual variability to drug treatment.
- Identification of biomarkers to implement the thrombotic risk stratification and to optimise drug therapy. A significant contribution of the Unit in this specific field of research has been the identification - never described before - of the expression of Tissue Factor by circulating human platelets isolated both from healthy volunteers and from patients with cardiovascular pathology. More recently, the long experience in flow cytometry has allowed to identify the fingerprint of circulating microvesicles as an interesting diagnostic and prognostic biomarker and tool that cardiologists can use to optimise drug therapy.
For these lines of research, the unit uses approaches ranging from cell biology to molecular biology and benefits from many years of experience in flow cytometry with a multi-parametric labeling of whole blood thus avoiding sample manipulation.
The members of the laboratory are holders of numerous grants from various national and international institutions (Cariplo 2015, Aspire 2016, PRIN 2017, Cariplo 2018, Cariplo 2019, MIND FoodS Hub 2019) that gave them the opportunity to collaborate with numerous research groups. In addition, since February 2018, Prof. Camera is the Chairperson of the Platelet Physiology Committee in the SSC-ISTH Scientific and Standardization Committee and she collaborates in drafting of the guidelines issued by this scientific society.
The laboratory is also involved in the MIND Foods HUB project funded by the Lombardy Region. This project aims to promote research at various levels in the agri-food sector and considered the driven force for innovation and development by integrating multidisciplinary skills and bringing together the experience of many excellent international research bodies and companies.