Today, it is known that the heart and vasculature are immunologically active organs. 
 
𝗞𝗲𝘆 𝗶𝗻𝘁𝗲𝗿𝗳𝗮𝗰𝗲𝘀 𝗼𝗳 𝗶𝗺𝗺𝘂𝗻𝗲–𝗰𝗮𝗿𝗱𝗶𝗼𝘃𝗮𝘀𝗰𝘂𝗹𝗮𝗿 𝗰𝗿𝗼𝘀𝘀𝘁𝗮𝗹𝗸 
𝟭) 𝗘𝗻𝗱𝗼𝘁𝗵𝗲𝗹𝗶𝗮𝗹 𝗶𝗺𝗺𝘂𝗻𝗼𝗹𝗼gy
Endothelial cells actively sense inflammatory cues and regulate immunity. Through expression of adhesion molecules (ICAM-1, VCAM-1, selectins), chemokines, and antigen-presenting machinery, endothelium controls immune cell recruitment and vascular inflammation [1]. 
 
𝟮) 𝗟𝗲𝘂𝗸𝗼𝗰𝘆𝘁𝗲 𝘁𝗿𝗮𝗳𝗳𝗶𝗰𝗸𝗶𝗻𝗴 
T cells, monocytes, and neutrophils traffic through blood vessels. Their extravasation is essential for host defense, while dysregulation contributes to chronic inflammatory disease. This trafficking is shaped by shear stress, endothelial activation, and cytokine gradients [2]. 
 
𝟯) 𝗔𝘁𝗵𝗲𝗿𝗼𝘀𝗰𝗹𝗲𝗿𝗼𝘀𝗶𝘀 𝗮𝘀 𝗮 𝗰𝗵𝗿𝗼𝗻𝗶𝗰 𝗶𝗺𝗺𝘂𝗻𝗲 𝗱𝗶𝘀𝗲𝗮𝘀𝗲 
Atherosclerosis is now recognized as an immune-driven pathology. Monocyte-derived macrophages, T cells, inflammasome activation, and cytokines such as IL-1β and TNF-α influence plaque formation, progression, and rupture [3]. 
 
𝟰) 𝗠𝘆𝗼𝗰𝗮𝗿𝗱𝗶𝗮𝗹 𝗶𝗻𝗳𝗮𝗿𝗰𝘁𝗶𝗼𝗻–𝗶𝗻𝗱𝘂𝗰𝗲𝗱 𝗶𝗺𝗺𝘂𝗻𝗲 𝗿𝗲𝗺𝗼𝗱𝗲𝗹𝗶𝗻𝗴 
After myocardial infarction (MI), massive immune remodeling occurs. Early innate immune responses drive debris clearance, while later adaptive responses shape fibrosis and repair. An imbalance in this immune program contributes to adverse remodeling and heart failure [4]. 
 
𝟱) 𝗦𝗼𝗹𝘂𝗯𝗹𝗲 𝗺𝗲𝗱𝗶𝗮𝘁𝗼𝗿𝘀 𝗶𝗻 𝗰𝗶𝗿𝗰𝘂𝗹𝗮𝘁𝗶𝗼𝗻 
Cytokines, chemokines, and the complement system circulate systemically, linking local tissue injury to whole-body immune responses. Complement activation is implicated in vascular inflammation [3]. 
 
6) Blood–𝗯𝗿𝗮𝗶𝗻 𝗯𝗮𝗿𝗿𝗶𝗲𝗿 (𝗕𝗕𝗕) 𝗮𝗻𝗱 𝗶𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝘆-𝗿𝗲𝗹𝗮𝘁𝗲𝗱 𝘁𝗼𝘅𝗶𝗰𝗶𝘁𝘆 
In CAR-T cell therapy, systemic cytokine release can disrupt endothelial integrity at the BBB, contributing to immune effector cell–associated neurotoxicity syndrome (ICANS). This highlights how vascular biology critically shapes immunotherapy safety profiles [5]. 
 
𝗤𝘂𝗲𝘀𝘁𝗶𝗼𝗻 𝗳𝗼𝗿 𝘁𝗵𝗲 𝗮𝘂𝗱𝗶𝗲𝗻𝗰𝗲 
Should future immunotherapies be co-designed with vascular-protective strategies to minimize cardiovascular and neurovascular toxicity? 
 
Stay tuned for 𝗗𝗮𝘆 𝟵𝟭: 𝗔𝗹𝗹𝗲𝗿𝗴𝗶𝗲𝘀 – 𝗙𝗿𝗼𝗺 𝗔𝗻𝘁𝗶𝗴𝗲𝗻 𝗘𝘅𝗽𝗼𝘀𝘂𝗿𝗲 𝘁𝗼 𝗜𝗺𝗺𝘂𝗻𝗲 𝗢𝘂𝘁𝗰𝗼𝗺𝗲 
 
𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀 
1. DOI: 10.1038/nri2171 
2. DOI: 10.1016/j.immuni.2014.10.008
3. DOI: 10.1038/nature01323 
4. DOI: 10.1016/j.phrs.2008.06.007 
5. DOI: 10.1158/2159-8290.CD-17-0698 
 
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