scholarly journals Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk

2020 ◽  
Vol 8 ◽  
Author(s):  
Almudena Veiga-Lopez ◽  
Visalakshi Sethuraman ◽  
Nastassia Navasiolava ◽  
Barbara Makela ◽  
Isoken Olomu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Vascular Calcification ◽  
Alkaline Phosphatase Activity ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Inorganic Pyrophosphate ◽  
Ectopic Mineralization ◽  
In Pregnancy

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.

LEUCOCYTE METABOLISM IN PREGNANCY

1960 ◽  
Vol XXXV (IV) ◽  
pp. 575-584 ◽  
Author(s):  
C. Borel ◽  
J. Frei ◽  
A. Vannotti
Keyword(s):  
Alkaline Phosphatase ◽  
Oxygen Consumption ◽  
Pregnant Women ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Lactate Production ◽  
Glucose Consumption ◽  
In Pregnancy

ABSTRACT Enzymatic studies, on leucocytes of pregnant women, show an increase of the alkaline phosphatase activity and a decrease of the glucose consumption and lactate production, as well as of proteolysis. The oxygen consumption, with succinate as substrate, does not vary.

Abstract 300: Leptin Promotes the Osteoblast Differentiation and Mineralization of Primary Cultures of Vascular Smooth Muscle Cells by Regulating GSK-3β

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Melec G Zeadin ◽  
Martin K Butcher ◽  
Geoff H Werstuck
Keyword(s):  
Alkaline Phosphatase ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Phosphatase Activity ◽  
Vascular Calcification ◽  
Alkaline Phosphatase Activity ◽  
Osteoblast Differentiation ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Gsk 3Β

Obesity is an independent risk factor for cardiovascular disease (CVD) although the precise molecular mechanisms that link obesity to CVD are not understood. Recent studies suggest that factors secreted by adipose tissue may play an adverse role in cardiovascular health. We have previously demonstrated that the adipocytokine, leptin, promotes vascular calcification in apolipoprotein E - deficient mice and that this increase in calcification is associated with an increase in the expression of several osteoblast-specific markers within the vessel wall. In an effort to understand the mechanism by which leptin exerts these effects, we cultured primary bovine aortic smooth muscle cells (BASMCs) in the presence of 0 to 2 μg/ml leptin for up to 12 days. Osteogenic differentiation of BASMCs was determined by an increase in the expression of osteoblast-specific markers, and the induction of both alkaline phosphatase activity and mineralization. Consistent with previous studies, we found that treatment of BASMCs with leptin induced osteoblast differentiation in a dose-dependent manner. To investigate the underlying mechanism, we examined changes in the expression levels of key factors implicated in osteoblast differentiation, including members of the Wnt signaling pathway. We found that exposure to leptin induced the Erk 1/2-dependent inactivation of GSK-3β, through Ser9 phosphorylation, and a subsequent increase in the nuclear accumulation of β-catenin. Transfection of BASMCs with an adenovirus that expressed constitutively active GSK-3β (Ad-GSK-3β S9A) resulted in a > 2-fold increase in GSK-3β activity, a decrease in the expression of the osteoblast-specific marker, osteopontin, and a significant decrease in leptin-induced alkaline phosphatase activity. Together, our results provide a possible mechanism by which elevated leptin concentrations, associated with obesity, promote osteoblast differentiation, and vascular calcification in vivo.

scholarly journals Endocrine-Disrupting Chemical Exposures in Pregnancy: a Sensitive Window for Later-Life Cardiometabolic Health in Women

2021 ◽  
Author(s):  
Emily S. Barrett ◽  
Susan W. Groth ◽  
Emma V. Preston ◽  
Carolyn Kinkade ◽  
Tamarra James-Todd
Keyword(s):  
Cardiovascular Disease ◽  
Maternal Obesity ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Later Life ◽  
Cardiometabolic Health ◽  
Endocrine Disrupting Chemical ◽  
Hypertensive Disorders ◽  
Endocrine Disrupting ◽  
In Pregnancy

Abstract Purpose of Review Pregnancy can be seen as a “stress test” with complications predicting later-life cardiovascular disease risk. Here, we review the growing epidemiological literature evaluating environmental endocrine-disrupting chemical (EDC) exposure in pregnancy in relation to two important cardiovascular disease risk factors, hypertensive disorders of pregnancy and maternal obesity. Recent Findings Overall, evidence of EDC-maternal cardiometabolic associations was mixed. The most consistent associations were observed for phenols and maternal obesity, as well as for perfluoroalkyl substances (PFASs) with hypertensive disorders. Research on polybrominated flame retardants and maternal cardiometabolic outcomes is limited, but suggestive. Summary Although numerous studies evaluated pregnancy outcomes, few evaluated the postpartum period or assessed chemical mixtures. Overall, there is a need to better understand whether pregnancy exposure to these chemicals could contribute to adverse cardiometabolic health outcomes in women, particularly given that cardiovascular disease is the leading cause of death in women.

Markers of cardiovascular disease risk after hypertension in pregnancy

2012 ◽  
Vol 30 (2) ◽  
pp. 351-358 ◽  
Author(s):  
George J. Mangos ◽  
Julia J. Spaan ◽  
Saiyini Pirabhahar ◽  
Mark A. Brown
Keyword(s):  
Cardiovascular Disease ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Hypertension In Pregnancy ◽  
In Pregnancy

scholarly journals Serum alkaline phosphatase is associated with arterial stiffness and 10‐year cardiovascular disease risk in a Chinese population

2021 ◽  
Author(s):  
Wen Guo ◽  
Xiaona Li ◽  
Juan Wu ◽  
Wenfang Zhu ◽  
Jing Lu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Alkaline Phosphatase ◽  
Arterial Stiffness ◽  
Roc Curve ◽  
Chinese Population ◽  
Disease Risk ◽  
Serum Alkaline Phosphatase ◽  
Subclinical Atherosclerosis ◽  
Cardiovascular Disease Risk ◽  
Cvd Risk

Abstract Background Serum alkaline phosphatase (ALP) has been recognized as a biomarker of cardiovascular disease (CVD) risk or mortality, recently. This study aimed to explore the association of ALP with arterial stiffness and 10-year CVD risk. Methods A total of 12539 participants without CVD who underwent health examinations including serum ALP level were retrospectively analyzed. Arterial stiffness was measured by brachial ankle pulse wave velocity (baPWV) and10-year CVD risk was evaluated by Framingham risk score (FRS). Results All participants were stratified into four groups according to the quartile of serum ALP. Participants with high ALP quartiles had higher cardiovascular parameters and baPWV, as well as an increase 10-year CVD risk. Logistic regression analysis showed that serum ALP was an independently risk factor for elevated baPWV and 10-year CVD risk after adjustment for traditional CVD risk factors in both women and men. In receiver operating characteristic (ROC) curve analysis, the area under the ROC curve (AUROC) of serum ALP for predicting elevated baPWV was 0.740 (95%CI 0.726–0.754, P < 0.001) in women, larger than that in men. Conclusions Serum ALP is independently associated with arterial stiffness and 10-year CVD risk in the general Chinese population. Our results also imply the better performance of serum ALP in women than men for predicting subclinical atherosclerosis.

scholarly journals Association of inorganic pyrophosphatase activity with normal calcification of rat costal cartilage in vivo

1969 ◽  
Vol 112 (4) ◽  
pp. 505-510 ◽  
Author(s):  
Nancy W. Alcock ◽  
Maurice E. Shils
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Inorganic Phosphate ◽  
Costal Cartilage ◽  
Hydrolytic Activity ◽  
Inorganic Pyrophosphatase ◽  
Inorganic Pyrophosphate ◽  
Pyrophosphatase Activity

1. Dialysed extracts of rat costal cartilage were shown to possess an enzyme that hydrolyses inorganic pyrophosphate. 2. Inorganic pyrophosphatase activity assayed in the presence of 2mm substrate was maximal at pH6·8. 3. Mg2+ was essential for activity, which was greatest with 10mm or higher concentrations of Mg2+. 4. Extracts prepared from cartilage taken from suckling rats (<20g.) showed little or no hydrolytic activity, but as rat weight increased inorganic pyrophosphatase activity was detected, increased to a maximum in tissue from animals weighing about 40g., and then rapidly declined. 5. The increase in inorganic pyrophosphatase activity was associated with an increase in the uptake of 45Ca by the cartilage in vivo. 6. Accumulation of calcium, inorganic phosphate and magnesium occurred when inorganic pyrophosphatase activity was at its maximum. 7. Alkaline phosphatase activity, measured in the same extracts used to determine pyrophosphatase activity, was highest in the tissues of the animals weighing <20g., and decreased as inorganic pyrophosphatase activity increased to its maximum. 8. There was no direct relationship between alkaline phosphatase activity and the onset of calcification.

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