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- Kiiskinen, Tuomo, et al.
(författare)
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Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases
- 2023
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 29:1, s. 209-218
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns of medication use in hyperlipidemia, hypertension and type 2 diabetes in up to 193,933 individuals (55% women) in the FinnGen study. In meta-analyses of up to 567,671 individuals combining FinnGen with the Estonian Biobank and the UK Biobank, we discovered 333 independent loci (P < 5 × 10–9) associated with medication use. Fine-mapping revealed 494 95% credible sets associated with the total number of medication purchases, changes in medication combinations or treatment discontinuation, including 46 credible sets in 40 loci not associated with the underlying treatment targets. The polygenic risk scores (PRS) for cardiometabolic risk factors were strongly associated with the medication-use behavior. A medication-use enhanced multitrait PRS for coronary artery disease matched the performance of a risk factor-based multitrait coronary artery disease PRS in an independent sample (UK Biobank, n = 343,676). In summary, we demonstrate medication-based strategies for identifying cardiometabolic risk loci and provide genome-wide tools for preventing cardiovascular diseases.
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| 2. |
- Räsänen, Matti, et al.
(författare)
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Carbon dioxide and methane fluxes from mounds of African fungus-growing termites
- 2023
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Ingår i: Biogeosciences. - 1726-4170. ; 20:19, s. 4029-4042
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Tidskriftsartikel (refereegranskat)abstract
- Termites play an essential role in decomposing dead plant material in tropical ecosystems and are thus major sources of gaseous C emissions in many environments. In African savannas, fungus-growing termites are among the ecologically most influential termite species. We studied the gas exchange from mounds of two closely related fungus-growing species (Macrotermes subhyalinus and M. michaelseni, respectively) in two habitats representing different vegetation types (grassland, bushland) together with soil fluxes around the mounds. The fluxes from active termite mounds varied from 120 to 2100 mg CO2-C m-2h-1 for carbon dioxide (CO2) and from 0.06 to 3.7 mg CH4-C m-2 h-1 for methane (CH4) fluxes. Mound CO2 fluxes varied seasonally with a 64 % decrease and 41 % increase in the fluxes from the dry to wet season at the grassland and bushland sites, respectively. During the wet season, the CO2 fluxes were significantly correlated with termite mound volume. The diurnal measurements from two M. michaelseni mounds suggest that the gas fluxes peak during the daytime, possibly reflecting changes in mound internal air circulation. Soil fluxes of both CO2 and CH4 were enhanced at up to 2 m distance from the mounds compared to the local soil respiration, indicating that, in addition to mound ventilation structures, a small proportion of the metabolic gases produced also leave the nest via surrounding soils.
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| 3. |
- Räsänen, Markus, et al.
(författare)
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VEGF-B Promotes Endocardium-Derived Coronary Vessel Development and Cardiac Regeneration
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 143:1, s. 65-77
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Tidskriftsartikel (refereegranskat)abstract
- Background:Recent discoveries have indicated that, in the developing heart, sinus venosus and endocardium provide major sources of endothelium for coronary vessel growth that supports the expanding myocardium. Here we set out to study the origin of the coronary vessels that develop in response to vascular endothelial growth factor B (VEGF-B) in the heart and the effect of VEGF-B on recovery from myocardial infarction.Methods:We used mice and rats expressing a VEGF-B transgene, VEGF-B-gene–deleted mice and rats, apelin-CreERT, and natriuretic peptide receptor 3–CreERT recombinase-mediated genetic cell lineage tracing and viral vector–mediated VEGF-B gene transfer in adult mice. Left anterior descending coronary vessel ligation was performed, and 5-ethynyl-2’-deoxyuridine–mediated proliferating cell cycle labeling; flow cytometry; histological, immunohistochemical, and biochemical methods; single-cell RNA sequencing and subsequent bioinformatic analysis; microcomputed tomography; and fluorescent- and tracer-mediated vascular perfusion imaging analyses were used to study the development and function of the VEGF-B–induced vessels in the heart.Results:We show that cardiomyocyte overexpression of VEGF-B in mice and rats during development promotes the growth of novel vessels that originate directly from the cardiac ventricles and maintain connection with the coronary vessels in subendocardial myocardium. In adult mice, endothelial proliferation induced by VEGF-B gene transfer was located predominantly in the subendocardial coronary vessels. Furthermore, VEGF-B gene transduction before or concomitantly with ligation of the left anterior descending coronary artery promoted endocardium-derived vessel development into the myocardium and improved cardiac tissue remodeling and cardiac function.Conclusions:The myocardial VEGF-B transgene promotes the formation of endocardium-derived coronary vessels during development, endothelial proliferation in subendocardial myocardium in adult mice, and structural and functional rescue of cardiac tissue after myocardial infarction. VEGF-B could provide a new therapeutic strategy for cardiac neovascularization after coronary occlusion to rescue the most vulnerable myocardial tissue.
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