Abstract:
:The contribution of plasma prekallikrein (PK) to vascular remodeling is becoming increasingly recognized. Plasma PK is activated when the zymogen PK is digested to an active enzyme by activated factor XII (FXII). Here, we present our findings that vascular smooth muscle cells (VSMC) activate plasma PK in the absence of FXII. Extracted plasma membrane and cytosolic fractions of VSMCs activate PK, but the rate of PK activation was greater by the membrane fraction. FXII neutralizing antibody did not affect PK activation by extracted proteins of VSMCs. VSMC PKA was inhibited by the serine protease inhibitors such as aprotinin, phenylmethylsulfonyl fluoride, leupeptin and CTI with CI50 of 0.78 μM, 1 mM, 3.13 μM and 40 nM on the cultured cells, respectively. No inhibition of PK activation by cysteine, aspartic acid, and metalloprotease inhibitors was observed. This is the first report of the presence of an intrinsic PKA in VSMC. Considering that VSMCs are normally separated from the circulating blood by endothelial cells, direct PK activation by VSMCs may play a role in disease states like diabetes, hyperlipidemia or hypertension where the endothelial layer is damaged.
journal_name
J Biol Regul Homeost Agentsjournal_title
Journal of biological regulators and homeostatic agentsauthors
Keum JS,Jaffa MA,Luttrell LM,Jaffa AAsubject
Has Abstractpub_date
2014-10-01 00:00:00pages
587-603issue
4eissn
0393-974Xissn
1724-6083pii
5journal_volume
28pub_type
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
pub_type: 杂志文章
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
pub_type: 杂志文章
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journal_title:Journal of biological regulators and homeostatic agents
pub_type: 临床试验,信件
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
pub_type: 临床试验,信件
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pub_type: 信件
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
pub_type: 临床试验,杂志文章
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
pub_type: 杂志文章
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
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journal_title:Journal of biological regulators and homeostatic agents
pub_type: 杂志文章
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