NOVEL CARDIAC MYOFILAMENT DESENSITIZING SUBSTANCE RELEASED BY ENDOCARDIAL CELLS
NOVEL CARDIAC MYOFILAMENT DESENSITIZING SUBSTANCE RELEASED BY ENDOCARDIAL CELLS
批准号:
3745560
负责人:
E LAKATTA
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
寻找心脏细胞功能的新型旁分泌调节剂。我们研究了
英文摘要
To search for novel paracrine modulators of heart cell function. We studied
the effects of effluent of superfused of normoxic and hypoxic endocardial
and vascular endothelial cultured cells on contraction and intracellular
calcium transients of isolated adult rat cardiac myocytes. We found that
EEC synthesize and release endothelin, which accounts for a positive
inotropic effect of sheep EEC effluent. Additionally, both endocardial and
vascular endothelial cells tonically release a novel substance which rapidl
and reversibly decreases the amplitude of myocytes twitch contraction by
inducing earlier relaxation, and also increase diastolic cell length. Thes
effects are not associated with any change in the intracellular calcium
transient, indicating cardiac myofilament "desensitization". The activity
of endothelial cell effluent remained stable at 37xC for several hours or a
4xC for at least 48 hours. The action of this substance did not involve
nitric oxide, cyclic GMP or prostanoids, nor changes in intracellular pH.
These properties suggest that endothelial cells may rapidly modulate cardia
contraction-relaxation coupling and diastolic tonus by altering myofilament
properties, as well as exert distant effects because of the unusual
stability of this substance. Superfusates of hypoxic endocardial and
vascular endothelial cells induced rapid, reversible reduction in myocyte
twitch amplitude (-67.0 q 4.9%; mean q S.E.M.), and decreased diastolic
length (-1.5q0.3fm; both P <0.001; n=18). Ca2+ transients were however
unchanged indicating altered myofilament properties. This effect was not
attributable to known endothelial agents, nor to changes in pH1 in SNARF-
loaded myocytes. Superfusate of hypoxic cells (to 1/20 dilution), but not
normoxic cells, completely and reversibly inhibited the in vitro sliding of
F-actin over rat cardiac myosin, and dramatically reduced actin-activated
myosin S1 ATPase activity. Neither effect was observed with smooth muscle
myosin. These data suggest a novel endothelial cell-mediated feed forward
mechanism which senses hypoxia and depresses myocyte contraction, by
releasing factors(s) that directly inhibit crossbridge cycling. This may
explain the clinical phenomenon of myocardial hibernation, i.e., depressed
contraction of viable myocardium during reduced coronary flow.
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会议论文
AGE ASSOCIATED CHANGES IN VASCULAR STIFFNESS PROPERTIES
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批准号:5200291
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
AGE ASSOCIATED CHANGES IN VASCULAR STIFFNESS PROPERTIES
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批准号:3745460
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
REGULATION OF LEFT VENTRICULAR VOLUMES AT REST AND DURING STRESS
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批准号:3789784
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
MECHANISM FOR SIGNAL TRANSDUCTION OF OPIOID RECEPTOR STIMULATION OF MYOCYTES
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批准号:3789781
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
AGE ASSOCIATED CHANGES IN VASCULAR PROPERTIES
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批准号:3802240
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
AGE ASSOCIATED CHANGES IN VASCULAR STIFFNESS PROPERTIES
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批准号:6160426
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
AGE ASSOCIATED CHANGES IN VASCULAR STIFFNESS PROPERTIES
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批准号:3789790
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
AGE ASSOCIATED CHANGES IN VASCULAR STIFFNESS PROPERTIES
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批准号:2565668
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
AUTONOMIC MODULATION OF RESTING AND EXERCISE CARDIAC PERFORMANCE
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批准号:3745459
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
AGE ASSOCIATED CHANGES IN VASCULAR STIFFNESS PROPERTIES
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批准号:3767790
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:E LAKATTA
-
依托单位:
REGULATION OF LEFT VENTRICULAR VOLUMES AT REST AND DURING STRESS
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批准号:3802234
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
REGULATION OF LEFT VENTRICULAR VOLUMES AT REST AND DURING STRESS
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批准号:3767787
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项目类别:
-
资助金额:$0.0万
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财政年份:--
-
负责人:E LAKATTA
-
依托单位:
MECHANISM FOR SIGNAL TRANSDUCTION OF OPIOID RECEPTOR STIMULATION OF MYOCYTES
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批准号:3767784
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E LAKATTA
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依托单位:
海外基金