hypothesis a b,c d arterial dissection e f progesterone
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Progesterone R.upregulation
Arterialdegredation
Arterydissection
Progesterone facilitates arterial extracellular matrix degradation and thereby dissection.
Hypothesis
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A, We first demonstrate that the progesterone receptor (PGR) is not specific to organs of the reproductive system andcan be found in vessels of male and female mice. B,C Vascular smooth muscle cells of Patients also harbour bothpopulations of the progesterone receptor. Furthermore a trend wise increase of PGR can be seen in patients whosuffered from an aneurism compared to healthy (HTX) controls. This suggest a link between PGR and vasculardiseases. D , Activation of the progesterone receptor in vitro leads to decreased migration and proliferation of Vascularsmooth muscle cells, a hallmark of impaired regeneration.
Spontaneous coronary artery dissection (SCAD) is the primary cause of myocardial infarction inyoung and pregnant women. The Patho-mechanism of SCAD is still unknown. In the uterus theProgesterone receptor facilitates vessel softening to facilitate oocyte Implantation andpregnancy. Accordingly this receptor was recently found in arteries of patients suffering from SCAD.We thereby came up with our hypothesis, that the vascular progesterone receptor mediates arterialsoftening and thereby dissection.
A
E, Activation of the progesterone receptor leads to genetic responses targeted at the extracellular matrix (ECM). F,Viral overexpression of the progesterone receptor and subsequent treatment with progesterone reveals,transcriptomic chances in ECM linked transcription factors, ECM modulation genes and dissection associated genes.Showing a distinct role of the progesterone receptor in vessel constitution and makeup.
E F
Highlights
The progesterone receptor is elevated in aneurismatic vessels, its activation inhibits regeneration,
induces extracellular matrix degradation and is tied to dissection associated genes.
PROGESTERONE PROMOTES SPONTANEOUS CORONARY ARTERY DISSECTIONHIRSCH J, VOLLAND A, NIKOLAJEVIC A, GRABER M, PÖLZL L, NÄGELE F, HILBE R, LECHNER S, HACKL H,
ENGLER C, TANCEVSKI , BEGLE J, GRIMM M, HOLFELD J, GOLLMANN-TEPEKÖYLÜ C.