PXD038236

PXD038236 is an original dataset announced via ProteomeXchange.

Title	LRP1 in Vascular Remodeling and Angiotensin Signaling
Description	Vascular smooth muscle cells (vSMC) exert a critical role in sensing and maintaining vascular integrity. These cells abundantly express the low-density lipoprotein receptor-related protein 1 (LRP1), a large endocytic and signaling receptor that recognizes numerous ligands including ApoE-rich lipoproteins, proteases, and protease-inhibitor complexes. We observed the spontaneous formation of aneurysms in the superior mesenteric artery (SMA) of both male and female mice in which LRP1 was genetically deleted in v SMC (smLRP1-/- mice). Quantitative proteomics revealed elevated abundance of several proteins in smLRP1-/- mice that are known to be induced by angiotensin II (AngII)-mediated signaling, suggesting that this pathway is dysregulated. Administration of losartan, an AngII type I receptor antagonist, or an angiotensinogen antisense oligonucleotide to reduce plasma angiotensinogen concentrations restored the normal SMA phenotype in smLRP1-/- mice and prevented aneurysm formation. Additionally, employing a vascular injury model, we noted excessive vascular remodeling and neointima formation in smLRP1-/- mice that was restored by losartan administration. Together, these findings reveal that LRP1 regulates vascular integrity and remodeling of the SMA by attenuating excessive AngII-mediated signaling.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:43:24.169.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brian Hampton
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-21 16:11:38	ID requested
1	2023-03-11 10:21:23	announced
⏵ 2	2023-11-14 08:43:29	announced	2023-11-14: Updated project metadata.

Zhang JM, Au DT, Sawada H, Franklin MK, Moorleghen JJ, Howatt DA, Wang P, Aicher BO, Hampton B, Migliorini M, Ni F, Mullick AE, Wani MM, Ucuzian AA, Lu HS, Muratoglu SC, Daugherty A, Strickland DK, LRP1 protects against excessive superior mesenteric artery remodeling by modulating angiotensin II-mediated signaling. JCI Insight, 8(2):(2023) [pubmed]

submitter keyword: ACE/Angiotensin Receptors/Renin Angiotensin System, Smooth Muscle Proliferation and Differentiation, Vascular Biology,LRP1, TGF-β, SMA Remodeling, Ang II, Hemodynamics, Remodeling, Animal Models of Human Disease, Proteomics, Smooth Muscle Cells

Dudley Strickland
contact affiliation	University of Maryland School of Medicine, Center for Vascular and Inflammatory Diseases
contact email	dstrickland@som.umaryland.edu
lab head
Brian Hampton
contact affiliation	University of Maryland School of Medicine
contact email	bhampton@som.umaryland.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038236
     1. Label: PRIDE project
     2. Name: LRP1 in Vascular Remodeling and Angiotensin Signaling