The Unit for the Study of Arterial Morphology and Function is focused on the non-invasive assessment of early atherosclerosis. Most studies are performed by using B-mode ultrasound, which provides information on the presence and extent of atherosclerotic plaques, arterial wall thickness (carotid intima media thickness or C-IMT) and vessel lumen diameter of superficial arteries. These variables are used as "surrogate" markers of atherosclerosis. The experience of the group is internationally recognized and the relevance ascribed to C-IMT by the scientific community is evidenced by the ever-growing number of studies which use this ultrasonic variable.
The general mission of the Unit is to identify new markers of arterial damage predictive of future vascular events and to produce the required scientific evidence to validate and transfer them from the research to the clinical practice. The Unit is strongly committed in developing new strategies for the better estimation of global cardiovascular risk based on the concept of "integrated biomarkers”. In this regard, the usefulness of the approach is documented by findings, showing that several of the identified variables (C-IMT, inter-adventitia common carotid diameter, fastest C-IMT progression etc.) not only associate to successive vascular events but also significantly improve the power of vascular risk factors to predict new vascular events, especially in the large number of patients who, according to available risk algorithms, fall into the intermediate-risk category.
Main research topics of the Unit are:
- identification of new atherosclerosis risk factors on the basis of their effect on C-IMT and endothelial function;
- development of new tools for the study of atherosclerosis and for improving predictability of vascular events;
- assessment of the association between C-IMT change over-time, conventional and emerging risk factors and the incidence of cardiovascular events;
- assessment of the effects of pharmacological treatments on morphological and functional properties of superficial arteries;
- identification of innovative methods for image processing based on artificial neural networks analyses;
- use of novel statistical models able to account for the complex patterns of interconnections between the different variables affecting cardiovascular disease;
- epidemiological studies aimed at identifying subjects at high risk of cardiovascular diseases.
In addition, the Unit coordinates and acts as core laboratory in national and international multicenter studies on the epidemiology of atherosclerosis.
High Resolution B-Mode Ultrasound Imaging
The general mission of our group is to increase the current knowledge of the pathophysiology of atherosclerotic diseases with the final goal to implement strategies aimed at reducing the incidence of cardio- and cerebro-vascular events and minimizing the related morbidities.
We are mainly interested in understanding whether these surrogate markers: (a) add independent information on risk or prognosis; (b) account for a clinically significant proportion of the disease, c) provide good sensitivity, specificity and predictive value in the prediction of cardiovascular events.
The strategy chosen to achieve these objectives is to use these markers from the earlier stages of the disease, well before the exordium of clinical manifestations.
→ Researches aimed at investigating the role of conventional and emerging atherosclerosis risk factors on the basis of their effect on C-IMT and endothelial function.
→ Research aimed at improving our current capacities to identify patients at high cardiovascular risk by using imaging techniques.
High Resolution B-Mode Ultrasound Imaging for the assessment of Mechanisms Involved in Atherosclerosis Progression
The general mission of our group in this field is to increase the current knowledge on carotid atherosclerotic progression with the final goal to understand the mechanism involved in the natural evolution of the disease as well as in the changes of this evolution induced by anti-atherosclerotic interventions.
In order to reach the Unit goals, our studies aim at:
- understanding the molecular and environmental mechanisms involved in atherosclerosis progression;
- investigating the possibility to interfere with this progression by using life-style and drug interventions.
More than 25 years of experience in the field have conferred to the Unit the role of Coordinator and Core Laboratory in national and international multicentre studies on the epidemiology of atherosclerosis.
Use of Artificial Neural Network for the Development of Innovative Diagnostic Systems for Atherosclerotic Disease
The general mission of our group in this field is to increase the current capacity to grasp hidden morphological features (e.g. wall information or plaque vulnerability) from QCA, MSCTA and ECU arterial images obtained with conventional computerized systems. In this direction, studies on the potential of innovative diagnostic tools based on ACMs are currently ongoing.
Specific aims of the project:
- To develop three innovative diagnostic tools, based on ACM systems, able to grasp hidden arterial wall features (e.g. position, dimension and/or calcifications of plaques etc) from QCA images (Tool-1), MSCTA images (Tool-2) and ECU images (Tool-3) not otherwise detectable in the original images.
- To evaluate the repeatability of image reprocessing as well as the measurement precision metric of novel arterial features extracted by QCA, MSCTA and ECU images by using ACM systems.
- To validate Tool-1, Tool-2 and Tool-3 by comparing the new arterial features extracted by ACM with the corresponding features detected by intravascular ultrasound (IVUS).
- Persson J, Strawbridge RJ, McLeod O, Gertow K, Silveira A, Baldassarre D, Van Zuydam N, Shah S, Fava C, Gustafsson S, Veglia F, Sennblad B, Larsson M, Sabater-Lleal M, Leander K, Gigante B, Tabak A, Kivimaki M, Kauhanen J, Rauramaa R, Smit AJ, Mannarino E, Giral P, Humphries SE, Tremoli E, de Faire U, Lind L, Ingelsson E, Hedblad B, Melander O, Kumari M, Hingorani A, Morris AD, Palmer CN, Lundman P, Ohrvik J, Soderberg S, Hamsten A. Sex-specific effects of adiponectin on carotid intima-media thickness and incident cardiovascular disease. J Am Heart Assoc.2015;4:e001853.
- Gaulton KJ, Ferreira T, Lee Y, Raimondo A, Magi R, Reschen ME, Mahajan A, Locke A, et al. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nat Genet 2015;47:1415-1425.
- Perisic LM, Rykaczewska U, Razuvaev A, Sabater-Lleal M, Lengquist M, Miller CL, Ericsson I, Rohl S, Kronqvist M, Aldi S, Magne J, Paloschi V, Vesterlund M, Li Y, Jin H, Diez MG, Roy J, Baldassarre D, Veglia F, Humphries SE, de Faire U, Tremoli E, Odeberg J, Vukojevic V, Lehtio J, Maegdefessel L, Ehrenborg E, Paulsson-Berne G, Hansson G, Lindeman JH, Eriksson P, Quertermous T, Hamsten A, Hedin U. Phenotypic modulation of smooth muscle cells in atherosclerosis is associated with downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM. Arterioscler Thromb Vasc Biol. 2016;36(9):1947-1961.
- Ehret GB, Ferreira T, Chasman DI, Jackson AU, Schmidt EM, Johnson T, Thorleifsson G, et al. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 2016;48:1171-1184.
- Strawbridge RJ, Hilding A, Silveira A, Osterholm C, Sennblad B, McLeod O, Tsikrika P, Foroogh F, Tremoli E, Baldassarre D, Veglia F, Rauramaa R, Smit AJ, Giral P, Kurl S, Mannarino E, Grossi E, Syvanen AC, Humphries SE, de Faire U, Ostenson CG, Maegdefessel L, Hamsten A, Backlund A. Soluble cd93 is involved in metabolic dysregulation but does not influence carotid intima-media thickness. Diabetes 2016;65:2888-2899.
Mauro Amato, Ph.D
Daniela Coggi, MSc
Beatrice Frigerio, Ph.D
Alessio Ravani, MSc
Daniela Sansaro, MSc