PXD038017

PXD038017 is an original dataset announced via ProteomeXchange.

Title	Calciprotein particles cause physiologically significant pro- inflammatory response in endothelial cells and systemic circulation
Description	Calciprotein particles (CPPs) represent self-assembling scavengers of excessive Ca2+ and PO43- ions which are formed in the human serum under the guidance of acidic proteins termed mineral chaperones (e.g., fetuin-A and albumin). While protecting the human organism from extraskeletal calcification, circulating CPPs are internalised by Kupffer cells and endothelial cells (ECs) and induce calcium stress upon their dissolution in lysosomes, thereby causing a pro-inflammatory response through the inflammasome-dependent and inflammasome-independent mechanisms. In patients with hyperphosphatemia (e.g., those with end-stage renal disease), a considerable proportion of primary amorphous CPPs transforms into secondary crystallised CPPs which instigate stronger cytokine release and indicate critical depletion of mineral buffering systems. A number of reports documented that serum of patients with chronic kidney disease, arterial hypertension, coronary artery disease, cerebrovascular disease, and autoimmune disorders shows increased CPP generation that reflects uncurbed mineral stress in these clinical scenarios and emphasizes the need in the development of anti-CPP therapies. For the experiments, CPPs are routinely synthesised in vitro by the supersaturation of serum-supplemented cell culture medium with Ca2+ and PO43- ions, as artificially generated CPPs are similar to those isolated from calcified human tissues. Approximate concentration of CPPs in the human blood is 250 particles per µL (2.5 × 108 per L), as measured by fluorescent-labeled bisphosphonate OsteoSense 680EX (IVISense Osteo 680 fluorescent probe). The kinetics of CPP assembling and clearance is far from being fully understood, albeit it evidently depends on the amount of Ca2+ and PO43- ions and acidic serum proteins (especially fetuin-A and albumin), and several reports specified a role of Mg2+ ions, HCO3- ions, and pyrophosphate in these processes as intrinsic Ca2+ antagonists. Although previous studies delineated cytokines overproduced by ECs under CPP treatment (i.e., interleukin-6, interleukin-8, and monocyte chemoattractant protein 1) and itemised other pathological consequences of CPP internalisation (i.e., hampered NO biosynthesis, endothelial-to-mesenchymal transition, and impaired mechanotransduction), a little is known about the proteomic signatures of ECs to calcium stress. Here we for the first time performed an unbiased proteomic profiling of ECs treated with CPPs and revealed relative enrichment of the protein categories related to mitochondrial and lysosomal physiology after the CPP treatment.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:58:51.259.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD038017
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Arseniy Lobov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-07 10:08:30	ID requested
1	2022-11-30 01:46:36	announced
⏵ 2	2023-11-14 08:58:51	announced	2023-11-14: Updated project metadata.

10.6019/PXD038017;

submitter keyword: Human, shotgun proteomics, TimsToF Pro, calciprotein particles, calcium, endothelium

Anton Kutikhin
contact affiliation	Head of the Laboratory for Vascular Biology, Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation
contact email	antonkutikhin@gmail.com
lab head
Arseniy Lobov
contact affiliation	Emmanuel Levy Lab, Dept. of Chemical and Structural Biology, Weizmann Institute of Science
contact email	arseniylobov@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038017
     1. Label: PRIDE project
     2. Name: Calciprotein particles cause physiologically significant pro- inflammatory response in endothelial cells and systemic circulation