Crit Rev Clin Lab Sci. 2013 May-Jun;50(3):79-89. doi: 10.3109/10408363.2013.813013.
Activation of sphingosine-1-phosphate signalling as a potential underlying mechanism of the pleiotropic effects of statin therapy.
Abstract
The mechanisms by which statins
are beneficial are incompletely understood. While the lowering of
low-density lipoprotein concentration is associated with regression of
atherosclerosis, the observed benefit of statin therapy begins within
months after its initiation, making regression an unlikely cause.
Although LDL-C lowering is the main mechanism by which statin therapy
reduces cardiovascular events, evidence suggests that at least some of
the beneficial actions of statins may be mediated by their pleiotropic effects. Thus, statins
may modulate the function of cardiovascular cells and key signalling
proteins, including small G-proteins, to ultimately exert their
pleiotropic effects. Sphingosine-1-phosphate
(S1P) is a naturally occurring bioactive lysophospholipid that
regulates diverse physiological functions in a variety of different
organ systems. Within the cardiovascular system, S1P mediates
cardioprotection following ischemia/reperfusion injury,
anti-inflammatory response, improvement of endothelial function,
increased mobilization and differentiation of endothelial progenitor
cells, inhibition of oxidation, and anti-atherogenic and anti-thrombotic
actions. Early evidence suggests that the pleiotropic effects of statins
may be related to an increase in S1P signalling. This review focuses on
S1P signalling as the potential mechanism underlying the pleiotropic
effects of statins. An improved understanding of this mechanism may be vital for establishing the clinical relevance of statins
and their importance in the treatment and prevention of coronary artery
disease. Key points Several studies have demonstrated a benefit from
lowering serum LDL-C with statins in patients with and without clinical evidence of CAD. These may be mediated by the pleiotropic effects of statins-the mechanisms of which are incompletely understood. Early evidence suggests that statins
may increase S1P signalling pathways through upregulation of the
expression of S1P receptors and an increase in plasma levels of S1P to
ultimately exert their pleiotropic effects. Future clinical trials and
basic science research aimed at the underlying mechanisms of the
pleiotropic effects of statins should enlighten us to their relative clinical relevance and importance.
- PMID:
- 23885725
- [PubMed - indexed for MEDLINE]
- Kommenttini.
- Sfingomyeliinin kataboliasta muodostuu S1P ja joskus luin että D-vitamiini säätelee Sfingomyeliinin kataboliaa. kun Statiini vaikuttaa vähentynyttä kolesterolia saattanee D-vitamiinia esiintyä liikkuvampana ja aktivoimassa SiP tietä- tosin kolesterolilla ei kai ole mitään salvage jräjestelmää edes plasmakalvorakenteessa kuten taas on esim sfingomyeleiinillä- ja niin vnahentunut kolesteroli vain irtoaa ja vapauttaa rasvaliukoista vitamiinia jota kerroksessa on., kun uutta kolesterolia ei setukaan kerrokseen yhtä paljon kuin ennen statiininv aikutuksesta- mikä tilanne siten pitää SiP ktabolisen tien aktivoituna. sillä kalvolipidienkin kesken vallitsee terve hierarkia. SM ei yksinään lisäänny jos ei muita kalvofosfolipidikomponentteja ja kolesterolia myös vastaavasti lisäänny.
- Sfingomyeliinin synteesipuolella vaadiittavat vitamiinit olivat K-vitamiini ja B6.
Inga kommentarer:
Skicka en kommentar