Ageing is currently the main untreated risk factor for cardiovascular diseases, while other treatment of risk factors such as hypercholesterolemia, and hypertension maximally prevent 50% of cardiovascular events such as myocardial infarction or stroke.2 3 As the number of people aged over 70 years reached 1 billion,1 ageing thus represents an unparalleled and neglected contribution to residual risk. In particular, vascular ageing is a major cause of death, increasing the risk of hypertension, atherosclerosis with ensuing heart attacks, and stroke.4 Importantly, it is now recognised that biological vascular age can be adjusted,5, 6 although chronological age marked by date of birth of course cannot change.
The known hallmarks of vascular ageing reflect changes in the two inner layers of the arteries, in the intima and media. Detrimental changes include intimal endothelial cell dysfunction, intima and media thickening, loss of medial vascular smooth muscle cell and elastin, accumulation of medial senescent cells and (mitochondrial) oxidative stress, deposition of medial collagen and/or calcification, together leading to vascular stiffness, loss of compliance and distensibility. The vascular effect of drugs targeting hallmarks of vascular ageing in (pre)clinical models is modest,7-9 and no successful treatment for human vascular ageing exists thus far. Furthermore, changes in the outer perivascular adventitia with human ageing are largely unknown, yet likely impactful. Finding a treatment for vascular ageing requires a better understanding of the early cellular and molecular mechanisms driving both the structural and functional changes of the aged vessel.
We now show in this project that perivascular cell function is crucial for maintaining vascular health during aging. This project thus provides the foundation and background knowledge on perivascular cell function in vascular ageing to lean on in subsequent translational therapeutic and diagnostic developments. Once we know more about the molecular changes in fibroblasts during ageing, a potential therapy will have a durable effect on improving healthy life expectancy, quality of life, and avoiding unnecessary treatments. However, the direct socioeconomic impact of the outcome of this fellowship are limited and the path to actual societal impact is long.
The impact for scientists in my field and other disciplines involving fibroblasts (organ fibrosis, oncology, tissue engineering, scleroderma) is evident as we provide new markers for fibroblasts. These scienctists will be reached via consortia and COST actions I participate in (incl. ERA-CVD, AtheroNL consortium, VascAge and AtheroNET COST action).. This stakeholder group will be informed via conferences, lectures, social media, and publication. Through my role as treasurer of EVBO, and affiliations in Edinburgh University and Aachen University, I will further inform scientists to integrate our new data into scientific practice, such as via the EVBO seminar series, and/or the annual women’s scientist’s festival (Maastricht University). The scientific community will have access to RNAseq data sets in repositories, and papers.
Medical physicians and their patients will also be impacted, and I will discuss future data with cardiovascular patients (Dutch Harteraad organisation) and their physicians how to best reach the target audience, hear what patient groups they feel would benefit, and to stimulate patient participation. I expect to organise workshops/lectures as done before, for instance at the cardiovascular grand rounds, Vascular surgeon network meetings, and hart&vaatcafé Limburg. The general public will be informed via outreach symposia, such as the Maastricht Arts&Science fair, Pint of Science, and/or Kidz college.
Stakeholders in the pharmaceutical industry will benefit from knowledge on biology and will be approached through key contact persons.
