"TRPV1 is a component of the atrial natriuretic signaling complex, and using orally delivered antagonists, presents a valid therapeutic target in the longitudinal reversal and treatment of cardiac hypertrophy and heart failure".
"TRPV1 is a component of the atrial natriuretic signaling complex, and using orally delivered antagonists, presents a valid therapeutic target in the longitudinal reversal and treatment of cardiac hypertrophy and heart failure".
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DOI：
10.1080/19336950.2018.1547611
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发表时间：
2019-12
期刊：
影响因子：
--
通讯作者：
Stokes AJ
中科院分区：
文献类型：
--
作者：
Horton JS;Shiraishi T;Alfulaij N;Small-Howard AL;Turner HC;Kurokawa T;Mori Y;Stokes AJ
心房利钠信号通路的激活是与一系列心血管疾病相关的病理反应所固有的，所述心血管疾病对心脏造成压力，特别是涉及持续心脏压力超负荷的那些，所述持续心脏压力超负荷诱导肥大和病理性重塑，所述病理性重塑经常导致心力衰竭。瞬时受体电位阳离子通道（TRPV1）是利钠肽A（natriuretic peptide A）、cGMP、PKG信号复合物的一个物理组分，与利钠肽受体1（NPR1）相互作用，并与其配体利钠肽A（natriuretic peptide A）结合（NPPA，ANP）TRPV1激活随后通过产生cGMP和PKG介导的TRPV1通道磷酸化而受到抑制。此外，用口服递送的药物抑制TRPV1抑制心室和肌细胞肥大，并且可以纵向改善暴露于由横向主动脉收缩诱导的慢性压力超负荷的小鼠的体内心脏功能，逆转由压力负荷诱导的预先建立的肥大，同时恢复心室功能。TRPV1是利钠肽信号传导系统的物理和调节组分，TRPV1抑制可能提供一种新的治疗策略，用于治疗和逆转与心脏肥大和心力衰竭相关的功能丧失。
Activation of the atrial natriuretic signaling pathway is intrinsic to the pathological responses associated with a range of cardiovascular diseases that stress the heart, especially those involved in sustained cardiac pressure overload which induces hypertrophy and the pathological remodeling that frequently leads to heart failure. We identify transient receptor potential cation channel, subfamily V, member 1, as a regulated molecular component, and therapeutic target of this signaling system. Data show that TRPV1 is a physical component of the natriuretic peptide A, cGMP, PKG signaling complex, interacting with the Natriuretic Peptide Receptor 1 (NPR1), and upon binding its ligand, Natriuretic Peptide A (NPPA, ANP) TRPV1 activation is subsequently suppressed through production of cGMP and PKG mediated phosphorylation of the TRPV1 channel. Further, inhibition of TRPV1, with orally delivered drugs, suppresses chamber and myocyte hypertrophy, and can longitudinally improve in vivo heart function in mice exposed to chronic pressure overload induced by transverse aortic constriction, reversing pre-established hypertrophy induced by pressure load while restoring chamber function. TRPV1 is a physical and regulated component of the natriuretic peptide signaling system, and TRPV1 inhibition may provide a new treatment strategy for treating, and reversing the loss of function associated with cardiac hypertrophy and heart failure.
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DOI：
10.1111/j.1549-8719.2010.00026.x
发表时间：
2010-05
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
--
作者：
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通讯作者：
Earley S
DOI：
10.1073/pnas.0407780102
发表时间：
2005-04-05
影响因子：
11.1
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Srivastava, P
影响因子：
9.5
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Kuhn, M
DOI：
10.1016/0735-1097(93)90468-g
发表时间：
1993-10-01
影响因子：
24
作者：
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通讯作者：
BURNETT, JC
影响因子：
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