Modulating Macrophage Polarization as a Therapy for Atherosclerosis

Macrophages are the cells responsible for removing cholesterols from blood vessel walls, to prevent the formation of fatty lesions. Unfortunately they become dysfunctional and inflammatory with age, as a result of rising levels of oxidized cholesterol. This leads to atherosclerosis, an ultimately fatal condition in which lesions grow to the point of weakening and narrowing blood vessels. This condition is strongly affected by inflammation, as macrophages can adopt different behavioral types, known as polarizations, in response to circumstances. Greater inflammatory signaling will drive more macrophages to adopt the aggressive M1 phenotype, focused on destroying pathogens, rather than the regenerative M2 phenotype that is more useful in removing cholesterol from blood vessel walls.

A number of groups are working on ways to force macrophages to adopt a specific phenotype, overriding their usual reaction to surrounding circumstances. In the research here, an approach is demonstrated to be beneficial in a mouse model of atherosclerosis, presumably by putting more macrophages back to work in lesions, clearing out lipids rather than flailing and adding to the inflammatory environment.

Atherosclerosis-related cardiovascular disease is still the predominant cause of death worldwide. Araloside C (AsC), a natural saponin, exerts extensive anti-inflammatory properties. In this study, we explored the protective effects and mechanism of AsC on macrophage polarization in atherosclerosis in vivo and in vitro. Using a high-fat diet (HFD)-fed ApoE-/- mouse model and RAW 264.7 macrophages exposed to oxidized LDL, AsC was evaluated for its effects on polarization and autophagy.

AsC significantly reduced the plaque area in atherosclerotic mice and lipid accumulation in oxidized-LDL-treated macrophages, promoted M2 phenotype macrophage polarization, increased the number of autophagosomes and modulated the expression of autophagy-related proteins. Moreover, the autophagy inhibitor 3-methyladenine and BECN1 siRNA obviously abolished the antiatherosclerotic and M2 macrophage polarization effects of AsC. Mechanistically, AsC targeted Sirt1 and increased its expression, and this increase in expression was associated with increased autophagy and M2 phenotype polarization. Altogether, AsC attenuates foam cell formation and lessens atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy.



Whether or not SENS will result in lifespans in thousands of years or hundreds. Whats sure this will lengthening life much. The world is becoming a better place every day. I don't want to miss out of this. I want to see the future. Im lucky and born in 78.

Posted by: Gekki at February 4th, 2020 10:00 AM

@Gekki: Agree. I don't want to miss out (dying of an accident or something). Beside og the music, video games and memories of the people I gown up with I would like to grow up to day. As the Norwegian king said it:

When I look back I see the landscape that I have walked through but it is different. All the great trees are gone. It seems there are remnants of them but it is the afterglow inside of you of all those you met who meant something in your life.
Olav Rex August 1977

Posted by: Norse at February 4th, 2020 10:06 AM

We are on the verge of slowing down be and even reverse some aspects of the aging. However, the therapies , even if they pass animal model now will take many years, if not decades, to be widely be available. So take good care of your body , so you have a better chance of making it.

Posted by: Cuberat at February 4th, 2020 11:52 AM

Whole body vibration

Whole Body Vibration-Induced Omental Macrophage Polarization and Fecal Microbiome Modification in a Murine Model.

Posted by: arren brandt at February 5th, 2020 11:57 AM
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