scholarly journals Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides: The same functional effect mediated by different cellular mechanisms

2017 ◽  
Vol 233 (4) ◽  
pp. 3230-3243 ◽  
Author(s):  
Jessal J. Patel ◽  
Dongxing Zhu ◽  
Britt Opdebeeck ◽  
Patrick D'Haese ◽  
José L. Millán ◽  
...  
2021 ◽  
Vol 224 (6) ◽  
pp. jeb237891
Author(s):  
Nathaly Hernández-Díaz ◽  
Francisca Leal ◽  
Martha Patricia Ramírez-Pinilla

ABSTRACTAn exceptional case of parallel evolution between lizards and eutherian mammals occurs in the evolution of viviparity. In the lizard genus Mabuya, viviparity provided the environment for the evolution of yolk-reduced eggs and obligate placentotrophy. One major event that favored the evolution of placentation was the reduction of the eggshell. As with all oviparous reptiles, lizard embryos obtain calcium from both the eggshell and egg yolk. Therefore, the loss of the eggshell likely imposes a constraint for the conservation of the egg yolk, which can only be obviated by the evolution of alternative mechanisms for the transport of calcium directly from the mother. The molecular and cellular mechanisms employed to solve these constraints, in a lizard with only a rudimentary eggshell such as Mabuya, are poorly understood. Here, we used RT-qPCR on placental and uterine samples during different stages of gestation in Mabuya, and demonstrate that transcripts of the calcium transporters trpv6, cabp28k, cabp9k and pmca are expressed and gradually increase in abundance through pregnancy stages, reaching their maximum expression when bone mineralization occurs. Furthermore, CABP28K/9K proteins were studied by immunofluorescence, demonstrating expression in specific regions of the mature placenta. Our results indicate that the machinery for calcium transportation in the Mabuya placenta was co-opted from other tissues elsewhere in the vertebrate bodyplan. Thus, the calcium transportation machinery in the placenta of Mabuya evolved in parallel with the mammalian placenta by redeploying the expression of similar calcium transporter genes.


2020 ◽  
Vol 21 (5) ◽  
pp. 1713 ◽  
Author(s):  
Owais M. Bhat ◽  
Xinxu Yuan ◽  
Sarah Camus ◽  
Fadi N. Salloum ◽  
Pin-Lan Li

Recent studies have shown that arterial medial calcification is mediated by abnormal release of exosomes/small extracellular vesicles from vascular smooth muscle cells (VSMCs) and that small extracellular vesicle (sEV) secretion from cells is associated with lysosome activity. The present study was designed to investigate whether lysosomal expression of mucolipin-1, a product of the mouse Mcoln1 gene, contributes to lysosomal positioning and sEV secretion, thereby leading to arterial medial calcification (AMC) and stiffening. In Mcoln1−/− mice, we found that a high dose of vitamin D (Vit D; 500,000 IU/kg/day) resulted in increased AMC compared to their wild-type littermates, which was accompanied by significant downregulation of SM22-α and upregulation of RUNX2 and osteopontin in the arterial media, indicating a phenotypic switch to osteogenic. It was also shown that significantly decreased co-localization of lysosome marker (Lamp-1) with lysosome coupling marker (Rab 7 and ALG-2) in the aortic wall of Mcoln1−/− mice as compared to their wild-type littermates. Besides, Mcoln1−/− mice showed significant increase in the expression of exosome/ sEV markers, CD63, and annexin-II (AnX2) in the arterial medial wall, accompanied by significantly reduced co-localization of lysosome marker (Lamp-1) with multivesicular body (MVB) marker (VPS16), suggesting a reduction of the lysosome-MVB interactions. In the plasma of Mcoln1−/− mice, the number of sEVs significantly increased as compared to the wild-type littermates. Functionally, pulse wave velocity (PWV), an arterial stiffening indicator, was found significantly increased in Mcoln1−/− mice, and Vit D treatment further enhanced such stiffening. All these data indicate that the Mcoln1 gene deletion in mice leads to abnormal lysosome positioning and increased sEV secretion, which may contribute to the arterial stiffness during the development of AMC.


2009 ◽  
Vol 75 (12) ◽  
pp. 1297-1307 ◽  
Author(s):  
Mohga M. El-Abbadi ◽  
Ashwini S. Pai ◽  
Elizabeth M. Leaf ◽  
Hsueh-Ying Yang ◽  
Bryan A. Bartley ◽  
...  

Life Sciences ◽  
2013 ◽  
Vol 93 (17) ◽  
pp. 646-653 ◽  
Author(s):  
Che Yu ◽  
Bing Chen ◽  
TingTing Zhao ◽  
Rong Wang ◽  
Javed Akhtar ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fang-Zheng Wang ◽  
Hong Zhou ◽  
Hong-Yu Wang ◽  
Hang-Bing Dai ◽  
Qing Gao ◽  
...  

Abstract Background Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (H2S) can prevent AMC in rats with diabetic nephropathy (DN). Methods DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague–Dawley rats for 8 weeks. Results Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a H2S donor, 50 μmol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous H2S generating enzyme activity and protein expression of cystathionine-γ-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-β1 protein level, and improved aortic elastin expression. Conclusions H2S may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-β1 level and increasing local elastin level.


2019 ◽  
Vol 39 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Bin Nie ◽  
Shao-ying Zhang ◽  
Si-ming Guan ◽  
Shao-qiong Zhou ◽  
Xin Fang

Endocrinology ◽  
2007 ◽  
Vol 148 (9) ◽  
pp. 4208-4216 ◽  
Author(s):  
Isabel R. Orriss ◽  
Jennifer C. Utting ◽  
Andrea Brandao-Burch ◽  
Kay Colston ◽  
Barbara R. Grubb ◽  
...  

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