PMID- 12805493
OWN - NLM
STAT- MEDLINE
DCOM- 20030801
LR  - 20220409
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 34
IP  - 7
DP  - 2003 Jul
TI  - Possible role of parathyroid hormone-related protein as a proinflammatory 
      cytokine in atherosclerosis.
PG  - 1783-9
AB  - BACKGROUND AND PURPOSE: Parathyroid hormone-related protein (PTHrP) is a 
      vasodilator peptide. In addition, PTHrP appears to affect vascular growth and to 
      be a mediator of inflammation in rheumatic and brain disorders. We examined the 
      possible role of PTHrP in the inflammatory process in atherosclerosis METHODS: We 
      immunohistochemically analyzed the cellular localization of PTHrP, the type 1 
      PTH/PTHrP receptor (PTH1R), and monocyte chemoattractant protein-1 (MCP-1) in 26 
      human carotid atherosclerotic plaques. RESULTS: The inflammatory region of 
      plaques was characterized by high PTHrP, PTH1R, and MCP-1 immunostaining in 
      relation to the cap (0.75+/-0.1 versus 0.29+/-0.04, 0.5+/-0.1 versus 0.25+/-0.05, 
      0.72+/-0.2 versus 0.29+/-0.05, respectively; P<0.05). PTHrP and MCP-1 were 
      colocalized in both resident and inflammatory cells in the plaque. Moreover, in 
      cultured vascular smooth muscle cells (VSMC), PTHrP(1-36) increased MCP-1 mRNA 
      (3-fold at 6 hours) and MCP-1 protein (2.5-fold at 24 hours). This effect was 
      inhibited by either PTHrP(7-34) or various protein kinase A inhibitors and by the 
      nuclear factor-kappaB (NF-kappaB) inhibitor parthenolide. Furthermore, 
      PTHrP(1-36) elicited an increase in NF-kappaB activation in VSMC. The 
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin inhibited 
      the PTHrP(1-36) induction of both NF-kappaB activity and MCP-1 overexpression, 
      and this was reversed by mevalonate. CONCLUSIONS: PTHrP appears to be a novel 
      proinflammatory mediator in the atheroma lesion and may contribute to the 
      instability of carotid atherosclerotic plaques. Our data provide a new rationale 
      to understand the mechanisms involved in the beneficial effects of statins in 
      atherosclerosis.
FAU - Martin-Ventura, Jose Luis
AU  - Martin-Ventura JL
AD  - Vascular Research Laboratory, Fundacion Jimenez Diaz, Autonoma University, 
      Madrid, Spain.
FAU - Ortego, Monica
AU  - Ortego M
FAU - Esbrit, Pedro
AU  - Esbrit P
FAU - Hernandez-Presa, Miguel Angel
AU  - Hernandez-Presa MA
FAU - Ortega, Luis
AU  - Ortega L
FAU - Egido, Jesus
AU  - Egido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030612
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (PTH1R protein, human)
RN  - 0 (PTHLH protein, human)
RN  - 0 (Parathyroid Hormone-Related Protein)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptide Hormones)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Parathyroid Hormone, Type 1)
RN  - 0 (Receptors, Parathyroid Hormone)
RN  - 0 (Sesquiterpenes)
RN  - 0 (parathyroid hormone-related peptide (1-36))
RN  - 2RDB26I5ZB (parthenolide)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Arteriosclerosis/immunology/*metabolism/pathology
MH  - Carotid Artery Diseases/immunology/*metabolism/pathology
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Cytokines/*metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Female
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
MH  - Immunohistochemistry
MH  - Inflammation Mediators/*metabolism
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/drug effects/metabolism
MH  - NF-kappa B/antagonists & inhibitors
MH  - Parathyroid Hormone-Related Protein
MH  - Peptide Fragments/pharmacology
MH  - Peptide Hormones/*metabolism
MH  - Precipitin Tests
MH  - Proteins/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptor, Parathyroid Hormone, Type 1
MH  - Receptors, Parathyroid Hormone/biosynthesis
MH  - Sesquiterpenes/pharmacology
EDAT- 2003/06/14 05:00
MHDA- 2003/08/02 05:00
CRDT- 2003/06/14 05:00
PHST- 2003/06/14 05:00 [pubmed]
PHST- 2003/08/02 05:00 [medline]
PHST- 2003/06/14 05:00 [entrez]
AID - 01.STR.0000078371.00577.76 [pii]
AID - 10.1161/01.STR.0000078371.00577.76 [doi]
PST - ppublish
SO  - Stroke. 2003 Jul;34(7):1783-9. doi: 10.1161/01.STR.0000078371.00577.76. Epub 2003 
      Jun 12.