Sickle cell anemia is a unique disease dominated by hemolytic anemia and vaso-occlusive events. The latter trigger a version of ischemia/reperfusion (I/R) pathobiology that is singular in its origin, cyclicity, complexity, instability, perpetuity, and breadth of clinical consequences. Specific clinical features are probably attributable to local I/R injury (e.g., stroke syndromes) or remote organ injury (e.g., acute chest syndrome) or the systematization of inflammation (e.g., multifocal arteriopathy). Indeed, by fashioning an underlying template of endothelial dysfunction and vulnerability, the robust inflammatory systematization no doubt contributes to all sickle pathology. In this Review, we highlight I/R–targeting therapeutics shown to improve microvascular blood flow in sickle transgenic mice undergoing I/R, and we suggest how such insights might be translated into human therapeutic strategies.
Bibliographical noteFunding Information:
The authors thank all the trainees and colleagues from our laboratories who participated in the experimental work cited here. The authors’ work has been supported by multiple NIH grants since 1978, most recently by HL55552 and HL114567.
Conflict of interest: RPH is a Scientific Advisory Board member for Emmaus Life Sciences and has a minor equity interest in Vanguard Therapeutics. JDB and GMV are consultants for and receive research funding from Hillhurst Biopharmaceuticals, CSL Behring, and Mitobridge/Astellas. Copyright: © 2020, American Society for Clinical Investigation. Reference information: J Clin Invest. 2020;130(3):1062–1072. https://doi.org/10.1172/JCI133639.
© 2020, American Society for Clinical Investigation.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural