Revealing Fates and Functions of Perivascular Macrophages during Restoration of Blood Perfusion following Injury

Here I introduce a new concept where macrophages in ischemic tissue change fate and adopt novel functions critical for blood flow restoration.Ischemic events cause rapid tissue damage and loss of function. Common causes include peripheral artery disease and myocardial infarction, but also organ transplantation.

These situations are characterized by shortage of oxygen supply as blood perfusion fails to meet the metabolic demand, resulting in ischemic injury and sterile inflammation.I propose that macrophages, which we find accumulate at perivascular positions in response to ischemic injury, perform a previously unknown cascade of functions and fate shifts crucial for blood flow reconstitution.

Thus, I hypothesize that perivascular macrophages and their progeny orchestrate (i) vessel maturation, (ii) blood flow regulation, and (iii) vessel pruning in ischemic tissues, making them essential for limiting tissue damage and supporting tissue restoration.

Here, I will test each of the proposed functions and establish if macrophages switch between these fates and functions during healing.

Further, I will investigate the origin of perivascular macrophages in ischemic tissue and determine what signals that drive these functional changes by combining transcriptomics with in vivo imaging and assessment of vascular function in genetically designed living mice.