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T. Kangas-Kontio, A. Huotari, H. Ruotsalainen, K.-H. Herzig, M. Tamminen, M. Ala-Korpela, M. J. Savolainen, S. Kakko
Genetic and environmental determinants of total and high-molecular weight adiponectin in families with low HDL-cholesterol and early coronary heart disease.
Atherosclerosis 2010, in press
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J. Pirkola, M. Vääräsmäki, M. Ala-Korpela, A. Bloigu, D. Canoy, A.-L. Hartikainen, M. Leinonen, S. Miettola, M. Paldanius, T. H. Tammelin, M.-R. Järvelin, A. Pouta
Low-grade, systemic inflammation in adolescents: Association with early life factors, gender and lifestyle.
American Journal of Epidemiology 171,
72-82,
2010
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L. S. Kumpula, S. M. Mäkelä, V.-P. Mäkinen, A. Karjalainen, J. M. Liinamaa, K. Kaski, M. J. Savolainen, M. L. Hannuksela, M. Ala-Korpela
Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps.
Journal of Lipid Research 51,
431-439,
2010
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The application of self-organizing maps to the combination of concentration and compositional lipoprotein data enabled data-driven lipoprotein phenotyping beyond the experimentally available classifications. Five different phenotypes are illustrated, all with characteristic plasma concentration profiles as well as distinct compositional features. In particular, deeper insight into the compositional variations in the lipoprotein particles appears a fundamental issue.
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P. Soininen, A. J. Kangas, P. Würtz, T. Tukiainen, T. Tynkkynen, R. Laatikainen, M.-R. Järvelin, M. Kähönen, T. Lehtimäki, J. Viikari, O. T. Raitakari, M. J. Savolainen, M. Ala-Korpela
High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism.
Analyst 134,
1781-1785,
2009
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V.-P. Mäkinen, C. Forsblom, L. M. Thorn, J. Wadén, K. Kaski, M. Ala-Korpela, P.-H. Groop
Network of vascular diseases, death and biochemical characteristics in a set of 4,197 patients with type 1 diabetes.
Cardiovascular Diabetology 8,
54,
2009
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M. Ala-Korpela, P. Soininen, M. J. Savolainen
Letter by Ala-Korpela et al Regarding article, "Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women".
Circulation 120,
e149,
2009
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K. Lähdesmäki, R. Plihtari, P. Soininen, E. Hurt-Camejo, M. Ala-Korpela, K. Öörni, P. T. Kovanen
Phospholipase A2 –modified LDL particles retain the generated hydrolytic products and are more atherogenic at acidic pH.
Atherosclerosis 207,
352-359,
2009
Objective: Hydrolysis of LDL by phospholipase A2 (PLA2) generates nonesterified fatty
acids (NEFAs) and lysophospholipids (lysoPCs). Binding of the PLA2-modified LDL to
proteoglycans, and their uptake by macrophages are increased. Since the extracellular pH is
decreased in advanced atherosclerotic plaques, we examined the effects of acidic pH on
PLA2-induced LDL modification and its proatherogenic consequences.
Results: sPLA2-V hydrolyzed LDL particles avidly at pH range 7.55.5. With decreasing pH,
the ability of albumin to sequester the formed NEFAs and lysoPCs from the
sPLA2-V-modified LDL particles decreased, and, as a consequence, more of the hydrolytic products
accumulated in the particles. At acidic pH, such sPLA2-V-modified LDL particles had higher
binding strength to human aortic proteoglycans, and their uptake by human monocytederived
macrophages and ensuing foam cell formation were enhanced.
Conclusions: The present data show that the proatherogenic effects exerted by
sPLA2-V-induced lipolysis of LDL are enhanced with decreasing pH and suggest that sPLA2-V is
particularly atherogenic in advanced atherosclerotic lesions, in which local acidic conditions
prevail.
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J. Niemi, V.-P. Mäkinen, J. Heikkonen, L. Tenkanen, Y. Hiltunen, M. L. Hannuksela, M. Jauhiainen, C. Forsblom, M.-R. Taskinen, Y. A. Kesäniemi, M. Savolainen, K. Kaski, P.-H. Groop, P. T. Kovanen, M. Ala-Korpela
Estimation of VLDL, IDL, LDL, HDL2, apoA-I and apoB from the Friedewald inputs – apoB and IDL, but not LDL, are associated with mortality in type 1 diabetes
Annals of Medicine 41,
451-461,
2009
Background. There is an unmet need to improve risk assessment of vascular diseases by lipoprotein profiling beyond plasma and LDL lipids.
Aims. (i) To study the relation of various lipoprotein lipid and apolipoprotein (apo) measures on the Friedewald inputs, i.e., plasma triglycerides (TG), cholesterol (TC), and HDL-C. (ii) Build up regression models for the appropriate measures based solely on the Friedewald inputs.
Methods. Data were available for 1,775 plasma samples from which VLDL, IDL, LDL and HDL were also isolated by ultracentrifugation. For HDL2-C and apolipoproteins 343 and 247 samples were available, respectively.
Results. Accurate models were obtained for VLDL-TG (cross-validation r=0.98), LDL-C (r=0.91), HDL2-C (r=0.92), apoA-I (r=0.92) and apoB (r=0.95). A semi-quantitative model was obtained for IDL-C (r=0.78). Due to the anticipated role of IDL-C in atherosclerosis, it was still kept within the accepted models and pursued further. The associations of the estimates with premature deaths were studied in 4,084 patients with type 1 diabetes. The behavior of IDL-C and LDL-C was markedly different, the best predictors of mortality being apoB, apoB to apoA-I ratio, and IDL-C.
Conclusions. The new models allow identification of clinically relevant lipoprotein profiles with no added cost to the conventional Friedewald formula.
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T. Liimatainen, J. M. Hakumäki, R. A. Kauppinen, M. Ala-Korpela
Monitoring of gliomas in vivo by diffusion MRI and 1H MRS during gene therapy induced apoptosis – interrelationships between water diffusion and mobile lipids
NMR in Biomedicine 22,
272-279,
2009
The measurement of water diffusion by diffusion-weighted MRI (DWI) in vivo offers a
non-invasive methodology to assess tissue responses to anti-cancer therapies. A
pathway for cell death following anti-cancer treatments is often apoptosis which leads to
accumulation of mobile lipids detectable by 1H MRS in vivo. However, it is not known
how these discrete MR markers of cell death relate to each other. Here, in a rodent
tumour model, i.e., ganciclovir-treated herpes simplex thymidine kinase (HSV-tk) gene
transfected BT4C gliomas; we studied the interrelationships between water diffusion
(Trace{D}) and mobile lipids during apoptosis. The water diffusion and the waterreferenced
concentrations of the mobile lipids showed clearly increasing and
interconnected trends during treatment. Of the accumulating 1H MRS-visible lipids, the
fatty acid –CH=CH– groups and the cholesterol compounds showed the strongest
associations with the water diffusion (r2 = 0.30; p < 0.05 and r2 = 0.48; p < 0.01,
respectively). These results indicate that the tumour histopathology and apoptotic
processes during tumour shrinkage can be interrelated in vivo via DWI of tissue water
and 1H MRS of the mobile lipids, respectively. However, there was considerable
individual variation in the associations, particularly at the end of the treatment period
and in the relative composition of the accumulating NMR-visible lipids. The findings
suggest that, the assessment of individual treatment response in vivo may benefit from
the combination of DWI and 1H MRS. The absolute and relative changes in the mobile
lipids could indicate initiation of tumour shrinkage even though changes in the tissue
water diffusion are still small. Conversely, heavily increased water diffusion most likely
indicates that substantial cell decomposition has taken place in the tumour tissue when the 1H MRS resonances of mobile lipids alone can no longer give a reliable estimate on
tissue conditions.
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T. Tukiainen, T. Tynkkynen, V.-P. Mäkinen, P. Jylänki, A. Kangas, J. Hokkanen, A. Vehtari, O. Gröhn, M. Hallikainen, H. Soininen, M. Kivipelto, P.-H. Groop, K. Kaski, R. Laatikainen, P. Soininen, T. Pirttilä, M. Ala-Korpela
A multi-metabolite analysis of serum by 1H NMR spectroscopy: early systemic signs of Alzheimer's disease
Biochemical and Biophysical Research Communications 375,
356-361,
2008
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V.-P. Mäkinen, C. Forsblom, L. Thorn, J. Wadén, D. Gordin, O. Heikkilä, K. Hietala, L. Kyllönen, J. Kytö, M. Rosengård-Bärlund, M. Saraheimo, N. Tolonen, M. Parkkonen, K. Kaski, M. Ala-Korpela, P.-H. Groop
Metabolic phenotypes, vascular complications and premature deaths in a population of 4,197 patients with type 1 diabetes
Diabetes 57,
2480-2487,
2008
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L. S. Kumpula, J. M. Kumpula, M.-R. Taskinen, M. Jauhiainen, K. Kaski, M. Ala-Korpela
Reconsideration of hydrophobic lipid distributions in lipoprotein particles
Chemistry and Physics of Lipids 155,
57-62,
2008
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S. M. Mäkelä, M. Jauhiainen, M. Ala-Korpela, J. Metso, T. M. Lehto, M. J. Savolainen, M. L. Hannuksela
HDL2 of heavy alcohol drinkers enhances cholesterol efflux from RAW-macrophages via enlarged phospholipid-rich HDL2b particles
Alcoholism: Clinical and Experimental Research 32,
991-1000,
2008
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V.-P. Mäkinen, P. Soininen, C. Forsblom, M. Parkkonen, P. Ingman, K. Kaski, P.-H. Groop, M. Ala-Korpela
1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death
Molecular Systems Biology 4,
167 (1-12),
2008
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M. Ala-Korpela
Critical evaluation of 1H NMR metabonomics of serum as a methodology for disease risk assessment and diagnostics
Clinical Chemistry and Laboratory Medicine 46,
27-42,
2008
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M. Ala-Korpela
The potential role of body fluid 1H NMR metabonomics as a prognostic and diagnostic tool
Expert Review of Molecular Diagnostics 7,
761-773,
2007
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P. Soininen, K. Öörni, H. Maaheimo, R. Laatikainen, P. T. Kovanen, K. Kaski, M. Ala-Korpela
1H NMR at 800 MHz facilitates detailed phospholipid follow-up during atherogenic modifications in low density lipoproteins
Biochemical and Biophysical Research Communications 360,
290-294,
2007
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A. Vehtari, V.-P. Mäkinen, P. P. Soininen. Ingman, S. M. Mäkelä, M. J. Savolainen, M. L. Hannuksela, K. Kaski, M. Ala-Korpela
A novel Bayesian approach to quantify clinical variables and to determine their spectroscopic counterparts in 1H NMR metabonomic data
BMC Bioinformatics 8,
(Suppl 2):S8,
2007
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V.-P. Mäkinen, P.-H. Groop, M. Ala-Korpela
Metabonomik – på väg mot individuell riskbedömning (in Swedish)
Finska Läkaresällskapets Handlingar 167,
40-46,
2007
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T. Suna, A. Salminen, P. Soininen, R. Laatikainen, P. Ingman, S. Mäkelä, M. J. Savolainen, M. L. Hannuksela, M. Jauhiainen, M.-R. Taskinen, K. Kaski, M. Ala-Korpela
1H NMR metabonomics of plasma lipoprotein subclasses - elucidation of metabolic clustering by self-organising maps
NMR in Biomedicine 20,
658-672,
2007
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M. Ala-Korpela, N. Lankinen, A. Salminen, T. Suna, P. Soininen, R. Laatikainen, P. Ingman, M. Jauhiainen, M.- R. Taskinen, K. Héberger, K. Kaski
The inherent accuracy of 1H NMR spectroscopy to quantify plasma lipoproteins is subclass dependent
Atherosclerosis 190,
352-358,
2007
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V.-P. Mäkinen, P. Soininen, C. Forsblom, M. Parkkonen, P. Ingman, K. Kaski, P.-H. Groop, M. Ala-Korpela
Diagnosing diabetic nephropathy by 1H NMR metabonomics of serum
Magnetic Resonance Materials in Physics, Biology and Medicine 19,
281-296,
2006
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T. Liimatainen, K. Lehtimäki, M. Ala-Korpela, J. Hakumäki
Identification of mobile cholesterol compounds in experimental gliomas by 1H MRS in vivo: effects of ganciclovir-induced apoptosis on lipids
FEBS Letters 580,
4746-4750,
2006
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M. Ala-Korpela, P. Sipola, K. Kaski
Molecular detection and characterisation of atherothrombosis by magnetic resonance - potential tools for individual risk assessment and diagnostics
Annals of Medicine 38,
322-336,
2006
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T. Suna, M. Hardey, J. Huhtinen, Y. Hiltunen, K. Kaski, J. Heikkonen, M. Ala-Korpela
Self-organising map approach to individual profiles: age, sex and culture in Internet dating
Sociological Research Online 11,
Issue 1,
2006
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K. Öörni, P. Posio, M. M. Ala-Korpela. Jauhiainen, P. T. Kovanen
Sphingomyelinase induces aggregation and fusion of small VLDL and IDL particles and increases their retention to human arterial proteoglycans
Arteriosclerosis, Thrombosis, and Vascular Biology 25,
1678-1683,
2005
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In relation to this paper, Arteriosclerosis, Thrombosis, and Vascular Biology
published an editorial by Kevin Jon Williams and Ira Tabas entitled
Lipoprotein retention — and clues for atheroma regression; Arterioscler Thromb Vasc Biol 25, 1536–1540, 2005.
(Article in PubMed)
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Mika Ala-Korpela, PhD
Professor in Computational Medicine
University of Oulu & Biocenter Oulu
Faculty of Medicine
Institute of Clinical Medicine
FI-90014 University of Oulu
Finland
Mobile: +358 40 1977 657
E-mail: 
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