PMID- 26908399
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20190110
IS  - 2047-9980 (Electronic)
IS  - 2047-9980 (Linking)
VI  - 5
IP  - 2
DP  - 2016 Feb 23
TI  - Varicose Remodeling of Veins Is Suppressed by 3-Hydroxy-3-Methylglutaryl Coenzyme 
      A Reductase Inhibitors.
LID - 10.1161/JAHA.115.002405 [doi]
LID - e002405
AB  - BACKGROUND: Despite the high prevalence of chronic venous insufficiency and 
      varicose veins in the Western world, suitable pharmaceutical therapies for these 
      venous diseases have not been explored to date. In this context, we recently 
      reported that a chronic increase in venous wall stress or biomechanical stretch 
      is sufficient to cause development of varicose veins through the activation of 
      the transcription factor activator protein 1. METHODS AND RESULTS: We 
      investigated whether deleterious venous remodeling is suppressed by the 
      pleiotropic effects of statins. In vitro, activator protein 1 activity was 
      inhibited by two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, 
      rosuvastatin and atorvastatin, in stretch-stimulated human venous smooth muscle 
      cells. Correspondingly, both statins inhibited venous smooth muscle cell 
      proliferation as well as mRNA expression of the activator protein 1 target gene 
      monocyte chemotactic protein 1 (MCP1). In isolated mouse veins exposed to an 
      increased level of intraluminal pressure, statin treatment diminished 
      proliferation of venous smooth muscle cells and protein abundance of MCP1 while 
      suppressing the development of varicose veins in a corresponding animal model by 
      almost 80%. Further analyses of human varicose vein samples from patients 
      chronically treated with statins indicated a decrease in venous smooth muscle 
      cell proliferation and MCP1 abundance compared with samples from untreated 
      patients. CONCLUSIONS: Our findings imply that both atorvastatin and rosuvastatin 
      effectively inhibit the development of varicose veins, at least partially, by 
      interfering with wall stress-mediated activator protein 1 activity in venous 
      smooth muscle cells. For the first time, this study reveals a potential 
      pharmacological treatment option that may be suitable to prevent growth of 
      varicose veins and to limit formation of recurrence after varicose vein surgery.
CI  - (c) 2016 The Authors. Published on behalf of the American Heart Association, Inc., 
      by Wiley Blackwell.
FAU - Eschrich, Johannes
AU  - Eschrich J
AD  - Division of Cardiovascular Physiology, Institute of Physiology and 
      Pathophysiology, Heidelberg University, Heidelberg, Germany.
FAU - Meyer, Ralph
AU  - Meyer R
AD  - Division of Cardiovascular Physiology, Institute of Physiology and 
      Pathophysiology, Heidelberg University, Heidelberg, Germany.
FAU - Kuk, Hanna
AU  - Kuk H
AD  - Division of Cardiovascular Physiology, Institute of Physiology and 
      Pathophysiology, Heidelberg University, Heidelberg, Germany.
FAU - Wagner, Andreas H
AU  - Wagner AH
AD  - Division of Cardiovascular Physiology, Institute of Physiology and 
      Pathophysiology, Heidelberg University, Heidelberg, Germany.
FAU - Noppeney, Thomas
AU  - Noppeney T
AD  - Versorgungszentrum fur Gefassmedizin, Nurnberg, Germany.
FAU - Debus, Sebastian
AU  - Debus S
AD  - Department of Vascular Medicine, German Aortic Center, Hamburg, Germany.
FAU - Hecker, Markus
AU  - Hecker M
AD  - Division of Cardiovascular Physiology, Institute of Physiology and 
      Pathophysiology, Heidelberg University, Heidelberg, Germany.
FAU - Korff, Thomas
AU  - Korff T
AD  - Division of Cardiovascular Physiology, Institute of Physiology and 
      Pathophysiology, Heidelberg University, Heidelberg, Germany 
      korff@physiologie.uni-heidelberg.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160223
PL  - England
TA  - J Am Heart Assoc
JT  - Journal of the American Heart Association
JID - 101580524
RN  - 0 (CCL2 protein, human)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Transcription Factor AP-1)
RN  - 83MVU38M7Q (Rosuvastatin Calcium)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Animals
MH  - Atorvastatin/*pharmacology
MH  - Case-Control Studies
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Muscle, Smooth, Vascular/*drug effects/metabolism/pathology
MH  - Myocytes, Smooth Muscle/*drug effects/metabolism/pathology
MH  - Rosuvastatin Calcium/*pharmacology
MH  - Signal Transduction/drug effects
MH  - Time Factors
MH  - Transcription Factor AP-1/genetics/metabolism
MH  - Varicose Veins/metabolism/pathology/*prevention & control
MH  - Vascular Remodeling/*drug effects
MH  - Veins/drug effects/metabolism/pathology
PMC - PMC4802467
OTO - NOTNLM
OT  - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
OT  - activator protein 1
OT  - smooth muscle cells
OT  - vascular remodeling
OT  - veins
EDAT- 2016/02/26 06:00
MHDA- 2016/12/15 06:00
PMCR- 2016/02/01
CRDT- 2016/02/25 06:00
PHST- 2016/02/25 06:00 [entrez]
PHST- 2016/02/26 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2016/02/01 00:00 [pmc-release]
AID - JAHA.115.002405 [pii]
AID - JAH31360 [pii]
AID - 10.1161/JAHA.115.002405 [doi]
PST - epublish
SO  - J Am Heart Assoc. 2016 Feb 23;5(2):e002405. doi: 10.1161/JAHA.115.002405.