TY - JOUR
T1 - Clonal Expansion in Cardiovascular Pathology
AU - Lin, Alexander
AU - Brittan, Mairi
AU - Baker, Andrew H.
AU - Dimmeler, Stefanie
AU - Fisher, Edward A.
AU - Sluimer, Judith C.
AU - Misra, Ashish
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Clonal expansion refers to the proliferation and selection of advantageous "clones" that are better suited for survival in a Darwinian manner. In recent years, we have greatly enhanced our understanding of cell clonality in the cardiovascular context. However, our knowledge of the underlying mechanisms behind this clonal selection is still severely limited. There is a transpiring pattern of clonal expansion of smooth muscle cells and endothelial cells - and, in some cases, macrophages - in numerous cardiovascular diseases irrespective of their differing microenvironments. These findings indirectly suggest the possible existence of stem-like vascular cells which are primed to respond during disease. Subsequent clones may undergo further phenotypic changes to adopt either protective or detrimental roles. By investigating these clone-forming vascular cells, we may be able to harness this inherent clonal nature for future therapeutic intervention. This review comprehensively discusses what is currently known about clonal expansion across the cardiovascular field. Comparisons of the clonal nature of vascular cells in atherosclerosis (including clonal hematopoiesis of indeterminate potential), pulmonary hypertension, aneurysm, blood vessel injury, ischemia- and tumor-induced angiogenesis, and cerebral cavernous malformations are evaluated. Finally, we discuss the potential clinical implications of these findings and propose that proper understanding and specific targeting of these clonal cells may provide unique therapeutic options for the treatment of these cardiovascular conditions.
AB - Clonal expansion refers to the proliferation and selection of advantageous "clones" that are better suited for survival in a Darwinian manner. In recent years, we have greatly enhanced our understanding of cell clonality in the cardiovascular context. However, our knowledge of the underlying mechanisms behind this clonal selection is still severely limited. There is a transpiring pattern of clonal expansion of smooth muscle cells and endothelial cells - and, in some cases, macrophages - in numerous cardiovascular diseases irrespective of their differing microenvironments. These findings indirectly suggest the possible existence of stem-like vascular cells which are primed to respond during disease. Subsequent clones may undergo further phenotypic changes to adopt either protective or detrimental roles. By investigating these clone-forming vascular cells, we may be able to harness this inherent clonal nature for future therapeutic intervention. This review comprehensively discusses what is currently known about clonal expansion across the cardiovascular field. Comparisons of the clonal nature of vascular cells in atherosclerosis (including clonal hematopoiesis of indeterminate potential), pulmonary hypertension, aneurysm, blood vessel injury, ischemia- and tumor-induced angiogenesis, and cerebral cavernous malformations are evaluated. Finally, we discuss the potential clinical implications of these findings and propose that proper understanding and specific targeting of these clonal cells may provide unique therapeutic options for the treatment of these cardiovascular conditions.
KW - cardiovascular diseases
KW - clonal expansion
KW - endothelial cells
KW - macrophages
KW - vascular smooth muscle cells
U2 - 10.1016/j.jacbts.2023.04.008
DO - 10.1016/j.jacbts.2023.04.008
M3 - (Systematic) Review article
SN - 2452-302X
VL - 9
SP - 120
EP - 144
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 1
ER -