Systemic and specific effects of antihypertensive and lipid-lowering medication on plasma protein biomarkers for cardiovascular diseases

Enroth, Stefan,1976-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik (författare)

A large fraction of the adult population is on lifelong medication for cardiovascular disorders, but the metabolic consequences are largely unknown. This study determines the effects of common anti-hypertensive and lipid lowering drugs on circulating plasma protein biomarkers. We studied 425 proteins in plasma together with anthropometric and lifestyle variables, and the genetic profile in a cross-sectional cohort. We found 8406 covariate-protein associations, and a two-stage GWAS identified 17253 SNPs to be associated with 109 proteins. By computationally removing variation due to lifestyle and genetic factors, we could determine that medication, per se, affected the abundance levels of 35.7% of the plasma proteins. Medication either affected a single, a few, or a large number of protein, and were found to have a negative or positive influence on known disease pathways and biomarkers. Anti-hypertensive or lipid lowering drugs affected 33.1% of the proteins. Angiotensin-converting enzyme inhibitors showed the strongest lowering effect by decreasing plasma levels of myostatin. Cell-culture experiments showed that angiotensin-converting enzyme inhibitors reducted myostatin RNA levels. Thus, understanding the effects of lifelong medication on the plasma proteome is important both for sharpening the diagnostic precision of protein biomarkers and in disease management.

Maturi, VarunUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Ludwiginstitutet för cancerforskning(Swepub:uu)varma720 (författare)
Berggrund, MalinUppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab(Swepub:uu)malbe459 (författare)
Bosdotter Enroth, SofiaMed Prod Agcy, POB 26, SE-75103 Uppsala, Sweden.(Swepub:uu)sofbo909 (författare)
Moustakas, AristidisUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Ludwiginstitutet för cancerforskning(Swepub:uu)arimo287 (författare)
Johansson, ÅsaUppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)asjoh108 (författare)
Gyllensten, Ulf B.Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)ulfgyll (författare)
Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Av författaren/redakt...: Enroth, Stefan, ...; Maturi, Varun; Berggrund, Malin; Bosdotter Enroth ...; Moustakas, Arist ...; Johansson, Åsa; visa fler...; Gyllensten, Ulf ...; visa färre...

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