Professional Education


  • Doctor of Philosophy, Karolinska Institutet (2018)
  • Master of Science, Karolinska Institutet (2012)
  • Bachelor of Science, Karolinska Institutet (2010)

All Publications


  • Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells. International journal of molecular sciences Carracedo, M., Persson, O., Saliba-Gustafsson, P., Artiach, G., Ehrenborg, E., Eriksson, P., Franco-Cereceda, A., Back, M. 2019; 20 (6)

    Abstract

    Autophagy serves as a cell survival mechanism which becomes dysregulated under pathological conditions and aging. Aortic valve thickening and calcification causing left ventricular outflow obstruction is known as calcific aortic valve stenosis (CAVS). CAVS is a chronic and progressive disease which increases in incidence and severity with age. Currently, no medical treatment exists for CAVS, and the role of autophagy in the disease remains largely unexplored. To further understand the role of autophagy in the progression of CAVS, we analyzed expression of key autophagy genes in healthy, thickened, and calcified valve tissue from 55 patients, and compared them with nine patients without significant CAVS, undergoing surgery for aortic regurgitation (AR). This revealed a upregulation in autophagy exclusively in the calcified tissue of CAVS patients. This difference in autophagy between CAVS and AR was explored by LC3 lipidation in valvular interstitial cells (VICs), revealing an upregulation in autophagic flux in CAVS patients. Inhibition of autophagy by bafilomycin-A1 led to a decrease in VIC survival. Finally, treatment of VICs with high phosphate led to an increase in autophagic activity. In conclusion, our data suggests that autophagy is upregulated in the calcified tissue of CAVS, serving as a compensatory and pro-survival mechanism.

    View details for DOI 10.3390/ijms20061486

    View details for PubMedID 30934548

  • Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation ATHEROSCLEROSIS Strawbridge, R. J., Silveira, A., den Hoed, M., Gustafsson, S., Luan, J., Rybin, D., Dupuis, J., Li-Gao, R., Kavousi, M., Dehghan, A., Haljas, K., Lahti, J., Gadin, J. R., Backlund, A., de Faire, U., Gertow, K., Giral, P., Goel, A., Humphries, S. E., Kurl, S., Langenberg, C., Lannfelt, L. L., Lind, L., Lindgren, C. M., Mannarino, E., Mook-Kanamori, D. O., Morris, A. P., de Mutsert, R., Rauramaa, R., Saliba-Gustafsson, P., Sennblad, B., Smit, A. J., Syvanen, A., Tremoli, E., Veglia, F., Zethelius, B., Bjorck, H. M., Eriksson, J. G., Hofman, A., Franco, O. H., Watkins, H., Jukema, J., Florez, J. C., Wareham, N. J., Meigs, J. B., Ingelsson, E., Baldassarre, D., Hamsten, A., IMPROVE Study Grp 2017; 266: 196–204

    Abstract

    Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.

    View details for DOI 10.1016/j.atherosclerosis.2017.09.031

    View details for Web of Science ID 000414069700027

    View details for PubMedID 29040868

    View details for PubMedCentralID PMC5679136