Molecular regulation of arterial aneurysms : Role of actin dynamics and microRNAs in vascular smooth muscle

• Aortic aneurysms are defined as an irreversible increase in arterial diameter by morethan 50% relative to the normal vessel diameter. The incidence of aneurysm rupture isabout 10 in 100,000 persons per year and ruptured arterial aneurysms inevitably resultsin serious complications, which are fatal in about 40% of cases. There is also a hereditarycomponent of the disease and dilation of the ascending thoracic aorta is often associatedwith congenital heart disease such as bicuspid aortic valves (BAV). Furthermore, specificmutations that have been linked to aneurysm affect polymerization of actin filaments.Polymerization of actin is important to maintain a contractile phenotype of smooth musclecells enabling these cells to resist mechanical stress on the vascular wall caused by theblood pressure according to the law of Laplace. Interestingly, polymerization of actin alsopromotes smooth muscle specific gene expression via the transcriptional co-activatorMRTF, which is translocated to the nucleus when released from monomeric actin. Inaddition to genes encoding for proteins involved in the contractile machinery, recentstudies have revealed that several non-coding microRNAs (miRNAs) are regulated bythis mechanism. The importance of these miRNAs for aneurysm development is onlybeginning to be understood. This review will summarize our current understanding aboutthe influence of smooth muscle miRNAs and actin polymerization for the developmentof arterial aneurysms.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Actin polymerization

Aneurysm

BAV

MicroRNA

Myocardin related transcription factors

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