The overall goal of the team consists of developing more effective strategies to treat congenital and acquired cardiovascular disease. Ongoing research also addresses diabetes-related microvascular complications, in particular impaired angiogenesis, and wound healing. To achieve these aims, the team is applying state of the art concepts in the field of therapeutic angiogenesis, cell therapy, gene/protein therapy, and cardiovascular tissue engineering.

One exemplar success of translation from bench research to clinical application and academic-industrial partnership is the discovery of human tissue kallikrein as a potent angiogenic factor reported by Madeddu in key Circulation and Circulation Research papers. This finding has incited clinical trials using crude kallikrein protein to treat thousand ischemic disease patients. This was followed by the development of recombinant kallikrein protein that the US-based DiaMedica Therapeutics has launched for the treatment of primary and recurrent stroke and renal disease. Likewise, Madeddu team has fostered the translation of the neuronal cell product frpm ReNeuron, a UK-based stem cell research company, for the treatment of stroke patients.

Madeddu is also recognized as a world leader in the field of pericytes as a target for reparative approaches based on the stimulation of endogenous arteriogenic potential and the manufacture of multi-cellularised vascular and valvular grafts. He collaborates with Caputo and Angelini to accelerate the transformation of new products in cardiac surgery applications with the ultimate goal of reducing the need for recurrent reconstructive operations.

Cardiovascular disease, especially ischemic heart disease, is a major cause of morbidity and mortality in the elderly.  Life-saving heart attack treatments have increased the number of patients who suffer from chronic sequalae and necessitate intensive treatment and frequent hospitalization. Therefore, Madeddu is developing curative modalities for preservation of the heart function through aging, such as replicating the successful program that confers long-living individuals with extended cardiovascular health. Madeddu has developed a long-lasting collaboration with Prof Annibale Puca from the University of Salerno, Italy, to study and exploit the longevity variant of the bactericidal/permeability-increasing fold-containing-family-B-member-4 gene (BPIFB4). Carriers of the longevity variant (LAV) express high levels of BPIFB4 in blood, which caracterise those with a better healthy status. In accordance, Madeddu and Puca demonstrated that high levels of circulating BPIFB4 protein protected against carotid stenosis and intima media thickness in human cohorts. LAV-BPIFB4 gene therapy showed anti-atherosclerotic, anti-hypertensive, pro-angiogenic, and neuroprotective activities, improving frailty indices, rescuing diabetic cardiomyopathy, and rejuvenating the immune system and vasculature. Moreover, replicating the preserved immune function of long living individuals, the LAV-BPIFB4 protein encouraged immunomodulatory responses by human myeloid cells.

Madeddu has published 190 papers and obtained multimillion grants from the Medical Research Council, British Heart Foundation, Heart Research UK, Diabetes UK, and the European Community since his relocation to Bristol in 2005 through a exceptional talent recruitment scheme. He is Chief Editor of Frontiers in Cardiovascular Biologics and Regenerative Medicine, Past Chief Editor of Vascular Biology, and Associated Editor of ATVB. He sits several International Grants Committees.

Yet, the achievement Madeddu is mostly proud consists of having fostered a new generation of raising stars in cardiovascular research, who, following Madeddu’s mentoring in Bristol, have reached a professorial status in different countries, including Nicolle Kränkel (Germany), Luciola Barcelos (Brasil), Rajesh Katare (New Zealand), Marco Meloni (France), Paola Campagnolo (UK), Ajman Al Haj Zen (Qatar). This meaning Bristol past-fellows are acting as ambassadors of the Bristol Heart Institute’s excellence across the world.