Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk.
Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk.
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DOI：
10.3389/fcell.2020.573727
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发表时间：
2020
影响因子：
5.5
通讯作者：
Szeri F
中科院分区：
文献类型：
--
作者：
Veiga-Lopez A;Sethuraman V;Navasiolava N;Makela B;Olomu I;Long R;van de Wetering K;Martin L;Aranyi T;Szeri F
流行病学研究表明，碱性磷酸酶活性升高与心血管疾病风险增加有关。其他流行病学数据表明，多胎分娩的母亲患晚发性心血管疾病的风险也增加。我们假设这两种关联源于一个共同的原因，即异位矿化抑制剂无机焦磷酸盐（碱性磷酸酶的底物）的血浆水平不足。由于碱性磷酸酶活性在妊娠期升高，我们假设焦磷酸盐浓度在妊娠期降低，可能导致经产妇血管钙化和心血管疾病风险增加。我们研究了血浆焦磷酸酶动力学前和产后的绵羊和在人类的术语，并证明其短缺在怀孕期间，反映碱性磷酸酶活性。接下来，我们测试了多产是否与弹性假黄瘤患者血管钙化增加有关，其特征是内源性血浆焦磷酸盐水平低。我们证明了这些患者在多次分娩时血管钙化增加。我们认为，重复怀孕期间焦磷酸盐的短暂短缺可能会导致血管钙化和多产相关的心血管疾病风险，威胁着全球数亿健康女性。需要进一步的试验来评估妊娠期补充焦磷酸盐是否可能是一种合适的预防性治疗，以减轻经产妇女的母体心血管疾病风险。
Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum in sheep and at term in humans and demonstrated its shortage in pregnancy, mirroring alkaline phosphatase activity. Next, we tested whether multiparity is associated with increased vascular calcification in pseudoxanthoma elasticum patients, characterized by low intrinsic plasma pyrophosphate levels. We demonstrated that these patients had increased vascular calcification when they give birth multiple times. We propose that transient shortages of pyrophosphate during repeated pregnancies might contribute to vascular calcification and multiparity-associated cardiovascular disease risk threatening hundreds of millions of healthy women worldwide. Future trials are needed to assess if gestational pyrophosphate supplementation might be a suitable prophylactic treatment to mitigate maternal cardiovascular disease risk in multiparous women.
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DOI：
10.1073/pnas.1319582110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Jansen, Robert S.;Kucukosmanoglu, Asli;van de Wetering, Koen
通讯作者：
van de Wetering, Koen
影响因子：
11.1
作者：
Dedinszki D;Szeri F;Kozák E;Pomozi V;Tőkési N;Mezei TR;Merczel K;Letavernier E;Tang E;Le Saux O;Arányi T;van de Wetering K;Váradi A
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Váradi A
DOI：
10.1016/j.jid.2015.10.065
发表时间：
2016-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Li Q;Arányi T;Váradi A;Terry SF;Uitto J
通讯作者：
Uitto J
影响因子：
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作者：
Hornstrup, Louise S.;Tybjaerg-Hansen, Anne;Frikke-Schmidt, Ruth
通讯作者：
Frikke-Schmidt, Ruth
影响因子：
3.7
作者：
Kunutsor, Setor K.;Bakker, Stephan J. L.;Dullaart, Robin P. F.
通讯作者：
Dullaart, Robin P. F.