
Professor Paolo Madeddu
Expertise
An international leader in cardiovascular regenerative medicine
Current positions
Professor of Experimental Cardiovascular Medicine
Bristol Medical School (THS)
Contact
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Biography
The overall goal of my present and future research consists of developing more effective strategies to treat limb and myocardial ischaemia and to improve the current methods employed for correction of cardiac defects in infants.
My own contribution has been the identification of novel angiogenic factors, human tissue kallikrein and nerve growth factor. In addition, I am looking at successful genetic programs that support health rather than trying to contrast pathogenic mechanisms. One example is our publications showing the therapeutic potential of transferring a gene variant associated with exceptional longevity to rescue diabetic cardiomyopathy, aging cardiomyopathy, and limb/myocardial ischemia. This genetic program has been “reviewed” by mother nature through thousand years , we are extending the success to the population at risk.
In recent years, my team has been working with Prof Caputo and Angelini to generate new tissue engineering solutions for correction of cardiac defects. We generated a prototype amedical product that Caputo is aiming to test in patients. We are moving to a second-generation product consisting of a hybrid (synthetic and natural material) topographically decorated with endothelial cells, vascular smooth muscle cells, and pericytes from the human umbilical cord to mimic a natural artery. The aim is to use this biocompatible system for correction of pulmonary artery defects. In collaboration with Angelini, we are manufacturing artificial valves decorated with microRNAs to accelerate the process of endothelialization.
Finally, we are conducting research on microvascular damage in COVID-19, with focus on spike protein induced signalling in human cardiac pericytes.
Research interests
The overall goal of my present and future research consists of developing more effective strategies to treat limb and myocardial ischaemia. My research also addresses diabetes-related microvascular complications, in particular impaired angiogenesis and wound healing. To achieve these aims, our group is applying state of the art concepts in the new field of therapeutic angiogenesis, which postulates that local delivery of growth factors that can promote clinically valuable increase in blood flow. Such growth factors are either delivered as proteins or as gene therapy. My own contribution has been the identification of novel angiogenic factors, in particular human tissue kallikrein and nerve growth factor, and developing platforms for translational research to bring these discoveries from the bench to the bedside. More recently, the idea has emerged that therapeutic angiogenesis can also be achieved using stem cell transplantation. We are currently engaged in studies aimed at challenging the therapeutic potentiality of human stem cells (embryonic, foetal, and adult) for the regeneration of wounded tissues in murine models of myocardial infarction and ischaemic diabetic wounds. In particular, we have funded plans to bring human pericytes to a first in man clinical trial by 2015.
A recent biography is available in the AHA Journal Circulation "European perspectives" at the URL http://circ.ahajournals.org/content/126/7/f37.full.pdf?ijkey=QdK5BJZZAQMZzVQ&keytype=ref
Projects and supervisions
Research projects
Healthy longevity gene inspired therapy to rescue cardiovascular disease in progeria
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
01/03/2022 to 29/02/2024
Targeting of protein kinase C beta II (PKCᄇII) to improve vascular and muscular fitness in diabetic peripheral ischaemia
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
25/04/2017 to 24/04/2020
Pump-Priming Award: Discovery of a novel angiomiR -miR-532- from screening of human pericytes
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
01/10/2016 to 30/09/2017
In vitro and in vivo preclinical testing of pericyte-engineered grafts for correction of congenital heart defects
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
01/07/2016 to 31/12/2019
SOCS BRITISH HEART FOUNDATION PG/15/
Principal Investigator
Managing organisational unit
Bristol Medical School (THS)Dates
31/05/2016
Thesis supervisions
Antigenic, functional and molecular characterization of human cardiac pericytes from newborn and grown-up congenital heart disease patients
Supervisors
Umbilical cord pericytes provide a viable option for neonatal vascular tissue engineering applications
Supervisors
Biomimetic Gelatin Nanofibrous Scaffolds for the Mechanical Modulation of Cardiac Pericyte Fate
Supervisors
Preclinical studies of swine pericytes for treatment of congenital and adult cardiac disease
Supervisors
Development of a new microRNA-functionalized composite scaffold as a valve substitute
Supervisors
Publications
Recent publications
02/06/2023The SARS-CoV-2 Spike protein: more than an entry key to heart damage
The SARS-CoV-2 Spike protein: more than an entry key to heart damage
The SARS-CoV-2 Spike protein modifies the transcriptional profile of human cardiac pericytes
Murine studies and expressional analyses of human cardiac pericytes reveal novel trajectories of SARS-CoV-2 Spike protein-induced microvascular damage
Signal Transduction and Targeted Therapy
The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy
Cardiovascular Research
The tyrosine kinase inhibitor Dasatinib reduces cardiac steatosis and fibrosis in obese, type 2 diabetic mice
Cardiovascular Diabetology
Teaching
I am involved in teaching MS and PhD students in several courses.