A recent study reveals that a common anti-acne drug can prevent chemical changes that cause arteries to harden. The respective study was carried out by scientists at the University of Cambridge and King’s College London, both in the United Kingdom. It states that the common antibiotic minocycline can prevent artery hardening by blocking PAR-triggered calcification.
The research basically focuses on the molecule called PAR-poly ADP-ribose. This molecule forms dense liquid droplets with calcium ions which then crystallize when they combine with elastic vascular tissues. This depositing of calcium, or calcification, cause the arterial tissues to harden.
The research was published in the journal Cell Reports.
Before this respective research, PAR was known for its role in DNA repair only. However, this respective research reveals that it also promotes calcification in arteries. The treatment tested in cell cultures and rats didn’t affect bone structures.
Tissue hardening is essential for healthy bone development. However, it can cause health problems when it occurs in arteries. Stiff, or hard, arteries hamper the flow of nourishing the blood to tissues and organs. It elevates the risk of conditions like
- High blood pressure
- Heart attack
- Dementia and other age-related diseases
Artery hardening is a common phenomenon observed in aged people. Until now there haven’t been any potential control or treatment regarding the condition.
How does calcification promote arterial hardening?
The research team explains that calcification hardens arteries and it commonly occurs at two sites in the blood vessel.
- Intima, or the tissue that lines the blood vessel wall.
- Media, or the tissue inside the blood vessel
Calcification at the former site occurs as part of atherosclerosis whereas, hardening of the media usually happens during aging. This respective research focused on what triggers the calcification, which takes the form of calcium phosphate crystals. The researchers work to find out why the deposits seem to concentrate around the collagen and elastin, which makes up much of the artery wall.
It was previously known that PAR can also operate outside the cells as a driver of bone tissue production. This led the scientists to wonder whether PAR could also have a role in calcification of other tissues. Moreover, when the cells undergo oxidative stress and DNA damage, they express two enzymes that produce PAR (PARP1 and PARP2).
The researchers used ultrastructural methods to see what happens at the molecular level when cells get stressed. They found that as the cells perish from oxidative stress, they export PAR. As mentioned above, PAR has a strong affinity to calcium ions thus it attaches firmly to calcium in preference to other minerals. Consequently, large calcium droplets are formed. These droplets attach to collagen and elastin and solidify into crystals, reducing elasticity and stiffening the arteries.
Minocycline to prevent tissue hardening
Next, the research team went to explore a way to hinder or hamper the process of tissue hardening. They looked for PARP inhibitors that block PAR production by blocking one of the enzymes that synthesize it. Interestingly, the researchers looked for inhibitors among the drugs that had already undergone trials in humans. This was done because it would shorten the development time for the use of the respective drug as a treatment to prevent stiff arteries.
The researchers identified and tested six molecules that fit their criteria and one of these were minocycline. It proved to be very effective at preventing arteries from becoming stiff in rats with long-term kidney disease. Note that Minocycline is generally prescribed to treat acne.
The team is working to conduct human trials of the treatment within the next 2 years as well. This research is highly significant as it revealed the mechanism behind artery calcification and also showed how it differs from bone calcification. Moreover, they have been able to identify a potential treatment to reduce blood vessel calcification as well.