干旱区生态环境知识资源中心(Arid): BCL11B Regulates Arterial Stiffness and Related Target Organ Damage

Arid

DOI	10.1161/CIRCRESAHA.120.316666
	BCL11B Regulates Arterial Stiffness and Related Target Organ Damage
	Valisno, Jeff Arni C.; May, Joel; Singh, Kuldeep; Helm, Eric Y.; Venegas, Lisia; Budbazar, Enkhjargal; Goodman, Jena B.; Nicholson, Christopher J.; Avram, Dorina; Cohen, Richard A.; Mitchell, Gary F.; Morgan, Kathleen G.; Seta, Francesca
通讯作者	Seta, F (corresponding author), Boston Univ, Sch Med, Dept Med, Vasc Biol Sect, 650 Albany St,X720, Boston, MA 02118 USA.
来源期刊	CIRCULATION RESEARCH
ISSN	0009-7330
EISSN	1524-4571
出版年	2021
卷号	128 期号:6 页码:755-768
英文摘要	Rationale: BCL11B (B-cell leukemia 11b) is a transcription factor known as an essential regulator of T lymphocytes and neuronal development during embryogenesis. A genome-wide association study showed that a gene desert region downstream of BCL11B, known to function as a BCL11B enhancer, harbors single nucleotide polymorphisms associated with increased arterial stiffness. However, a role for BCL11B in the adult cardiovascular system is unknown. Objective: Based on these human findings, we sought to examine the relation between BCL11B and arterial function. Methods and Results: Here we report that BCL11B is expressed in the vascular smooth muscle where it regulates vascular stiffness. RNA sequencing of aortas from wild-type and Bcl11b null mice (BSMKO) identified the cGMP (cyclic guanosine monophosphate)-cGMP-dependent protein kinase G (PKG) as the most significant differentially regulated signaling pathway in BSMKO compared with wild-type mice. BSMKO aortas showed decreased levels of PKG1, increased levels of Ca++-calmodulin-dependent serine/threonine phosphatase calcineurin (PP2B) and decreased levels of their common phosphorylation target, phosphorylated vasodilator-stimulated phosphoprotein (pVASP(S239)), a regulator of cytoskelatal actin rearrangements. Decreased pVASP(S239) in BSMKO aortas was associated with increased actin polymerization (filamentous/globular actin ratio). Functionally, aortic force, stress, wall tension, and stiffness, measured ex vivo in organ baths, were increased in BSMKO aortas, and BSMKO mice had increased pulse wave velocity, the in vivo index of arterial stiffness. Despite having no effect on blood pressure or microalbuminuria, increased arterial stiffness in BSMKO mice was associated with increased incidence of cerebral microbleeds compared with age-matched wild-type littermates. Conclusions: We have identified vascular smooth muscle BCL11B as a crucial regulator of aortic smooth muscle function and a potential therapeutic target for vascular stiffness.
英文关键词	actins blood pressure calcineurin phosphorylation vascular smooth muscle vascular stiffness
类型	Article
语种	英语
开放获取类型	Green Published, hybrid
收录类别	SCI-E
WOS记录号	WOS:000639308800009
WOS关键词	VASCULAR SMOOTH-MUSCLE ; PULSE-WAVE VELOCITY ; MICROFILAMENT PROTEIN VASP ; SYSTOLIC BLOOD-PRESSURE ; ALL-CAUSE MORTALITY ; CARDIOVASCULAR EVENTS ; AORTIC STIFFNESS ; FOCAL ADHESION ; GENE/ENVIRONMENT SUSCEPTIBILITY ; MYOSIN PHOSPHORYLATION
WOS类目	Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
WOS研究方向	Cardiovascular System & Cardiology ; Hematology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/349853
作者单位	[Valisno, Jeff Arni C.; May, Joel; Venegas, Lisia; Budbazar, Enkhjargal; Goodman, Jena B.; Cohen, Richard A.; Seta, Francesca] Boston Univ, Sch Med, Dept Med, Vasc Biol Sect, 650 Albany St,X720, Boston, MA 02118 USA; [Singh, Kuldeep; Nicholson, Christopher J.; Morgan, Kathleen G.] Boston Univ, Sargent Coll, Dept Hlth Sci, Boston, MA 02118 USA; [Helm, Eric Y.; Avram, Dorina] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL USA; [Avram, Dorina] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL USA; [Mitchell, Gary F.] Cardiovasc Engn, Norwood, MA USA
推荐引用方式 GB/T 7714	Valisno, Jeff Arni C.,May, Joel,Singh, Kuldeep,et al. BCL11B Regulates Arterial Stiffness and Related Target Organ Damage[J],2021,128(6):755-768.
APA	Valisno, Jeff Arni C..,May, Joel.,Singh, Kuldeep.,Helm, Eric Y..,Venegas, Lisia.,...&Seta, Francesca.(2021).BCL11B Regulates Arterial Stiffness and Related Target Organ Damage.CIRCULATION RESEARCH,128(6),755-768.
MLA	Valisno, Jeff Arni C.,et al."BCL11B Regulates Arterial Stiffness and Related Target Organ Damage".CIRCULATION RESEARCH 128.6(2021):755-768.