Reno-cardiovascular disease and regeneration: focus on interactions with the immune system

Abstract

Reno-cardiovascular diseases (reno-CVD) are characterized by a vicious cycle of injury to the kidneys, heart and blood vessels. Risk factors for CVD, including kidney disease and obesity, probably lead to similar disease processes. Primarily, processes related to inflammation, fibrosis and regeneration appear important. The goal of this thesis was to gain insight in how the interplay between these processes in reno-CVD-models influences organ function and how we can improve regenerative medicine (RM) strategies with this knowledge. Specifically, we investigated the role of macrophages (immune cells) and their potential contribution in realizing novel CVD treatments. Within RM, in situ (in place) tissue engineering (TE) is promising. Here, a synthetic design in any shape directly replaces non-functional tissue such as a blood vessel, followed by tissue rebuilding based on natural inflammation-driven regeneration. The question remains whether in situ TE in patients with reno-CVD, where inflammation and regeneration appear dysregulated, is efficient. Our cell-, animal- and dataset-models showed a broad array of effects on macrophage-driven inflammation, fibrosis and regeneration. They primarily appear to be regulated independently. Even though transient inflammation is crucial for wound healing, chronic inflammation is detrimental to organ function. Tailored treatments therefore appear to be recommended for reno-CVD patients. For instance, we can target the macrophage’s metabolism, mediating the transition from inflammation to regeneration. Concerning in situ TE, the characteristics of the degradable synthetic material appear more important than the presence of CVD. Adaptation to the material’s surface could contribute to improved function of (blood vessel) tissue.