R. Kivela - Academia.edu (original) (raw)

Papers by R. Kivela

Research paper thumbnail of Molecular adaptations of voltage-gated sodium ion channel related proteins after fatiguing stretch-shortening cycle exercise

Scandinavian journal of medicine & science in sports, 2008

Dystrophin associated protein alpha-syntrophin is known to interact with voltage-gated sodium ion... more Dystrophin associated protein alpha-syntrophin is known to interact with voltage-gated sodium ion channel (NaCh). Dystrophin is known to be sensitive to eccentric muscle actions. For this reason, the function of the NaChs might also be affected. Molecular adaptations of dystrophin, alpha-syntrophin and NaChs were investigated after fatiguing stretch-shortening cycle (SSC) exercise, which consisted of unilateral jumps on a sledge apparatus. Muscle biopsies were taken from the vastus lateralis muscle of eight healthy subjects immediately after (IA) and 2 days after (2D) the exercise to analyze mRNA levels and immunohistochemical staining patterns. SSC exercise resulted in decreased isometric maximal voluntary contraction (IA: -31+/-9%, 2D: -14+/-16%) and a delayed increase of plasma creatine kinase activity (2D: +178+/-211%). Despite muscle soreness (P<0.001), no morphological damage was observed and no changes were found in the mRNA concentrations. However, the relative changes of...

Research paper thumbnail of Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle

The FASEB Journal, 2006

Diabetes alters microvascular structure and function and is a major risk factor for cardiovascula... more Diabetes alters microvascular structure and function and is a major risk factor for cardiovascular diseases. In diabetic skeletal muscle, impaired angiogenesis and reduced VEGF-A expression have been observed, whereas in healthy muscle exercise is known to have opposite effects. We studied the effects of type 1 diabetes and combined exercise training on angiogenic mRNA expression and capillarization in mouse skeletal muscle. Microarray and real-time PCR analyses showed that diabetes altered the expression of several genes involved in angiogenesis. For example, levels of proangiogenic VEGF-A, VEGF-B, neuropilin-1, VEGFR-1, and VEGFR-2 were reduced and the levels of antiangiogenic thrombospondin-1 and retinoblastoma like-2 were increased. Exercise training alleviated some of these changes, but could not completely restore them. VEGF-A protein content was also reduced in diabetic muscles. In line with the reduced levels of VEGF-A and other angiogenic factors, and increased levels of angiogenesis inhibitors, capillary-to-muscle fiber ratio was lower in diabetic mice compared to healthy controls. Exercise training could not restore capillarization in diabetic mice. In conclusion, these data illustrate that type 1 diabetes is associated with reduced skeletal muscle capillarization and the dysregulation of complex angiogenesis pathways.-Kivelä, R., Silvennoinen, M., Touvra, A.-M., Lehti, T. M., Kainulainen, H., Vihko, V. Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle. FASEB J. 20, E921-E930 (2006) Key Words: angiogenesis ⅐ hyperglycemia ⅐ growth factor ⅐ VEGF E921 0892-6638/06/0020-0921 © FASEB E922 Vol. 20 June 2006 KIVELÄ ET AL. The FASEB Journal E923 DIABETES, EXERCISE TRAINING, AND ANGIOGENESIS Gene expressions are expressed in relation to the control group at the same time point. Statistically significant changes are color-coded: red ϭ up-regulated (two-based log of ratio (sample/control) Ն0.3 and PՅ0.0025), green ϭ down-regulated (two-based log of ratio (sample/control) Յ-0.3 and PՆ0.9975), yellow ϭ diabetes-induced change in expression was attenuated by exercise (significant change in expression in opposite direction in comparisons DT vs. D and D vs. C). Group abbreviations: D ϭ diabetic, DT ϭ diabetic trained, and T ϭ healthy trained, numbers ϭ time of the treatment in weeks.

Research paper thumbnail of CCBE1 Enhances Lymphangiogenesis via ADAMTS3-Mediated VEGF-C Activation

Research paper thumbnail of Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation

Research paper thumbnail of Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle

AJP: Heart and Circulatory Physiology, 2007

Blood and lymphatic vessels form together the circulatory system allowing the passage of fluids a... more Blood and lymphatic vessels form together the circulatory system allowing the passage of fluids and molecules within the body. Recently we showed that lymphatic capillaries are also found in the capillary bed of skeletal muscle. Exercise is known to induce angiogenesis in skeletal muscle, but it is not known whether exercise has effects on lymphangiogenesis or lymphangiogenic growth factors. We studied lymphatic vessel density and the expression of the main lymphangiogenic growth factors VEGF-C, VEGF-D, and their receptor VEGFR-3 in response to acute running exercise and endurance exercise training in the skeletal muscle of healthy and diabetic mice. VEGF-C mRNA expression increased after the acute exercise bout (P < 0.05) in healthy muscles, but there was no change in diabetic muscles. VEGF-C levels were not changed either in healthy or in diabetic muscle after the exercise training. Neither acute exercise nor exercise training had an effect on the mRNA expression of VEGF-D or VEGFR-3 in healthy or diabetic muscles. Lymphatic vessel density was similar in sedentary and trained mice and was more than 100-fold smaller than blood capillary density. Diabetes increased the mRNA expression of VEGF-D (P < 0.01).

Research paper thumbnail of Effects of streptozotocin-induced diabetes and physical training on gene expression of titin-based stretch-sensing complexes in mouse striated muscle

AJP: Endocrinology and Metabolism, 2006

Research paper thumbnail of Effects of exhaustive stretch-shortening cycle exercise on muscle blood flow during exercise

Acta Physiologica, 2006

The influence of exhaustive stretch-shortening cycle exercise (SSC) on skeletal muscle blood flow... more The influence of exhaustive stretch-shortening cycle exercise (SSC) on skeletal muscle blood flow (BF) during exercise is currently unknown. Quadriceps femoris (QF) BF was measured in eight healthy men using positron emission tomography before and 3 days after exhaustive SSC exercise. The SSC protocol consisted of maximal and submaximal drop jumps with one leg. Needle biopsies of the vastus lateralis muscles were taken immediately and 2 days after SSC for muscle endothelial nitric oxide synthase (eNOS) and interleukin-1-beta (IL-1beta) mRNA level determinations. All subjects reported subjective muscle soreness after SSC (P &amp;amp;amp;amp;lt; 0.001), which was well in line with a decrease in maximal isometric contraction force (MVC) and increase in serum creatine kinase activity (CK) (P = 0.018). After SSC muscle BF was 25% higher in entire QF (P = 0.043) and in its deep and superficial muscle regions, whereas oxygen uptake remained unchanged (P = 0.893). Muscle biopsies revealed increased IL-1beta (30 min: 152 +/- 75%, P = 0.012 and 2 days: 108 +/- 203%, P = 0.036) but decreased or unchanged eNOS (30 min; -21 +/- 57%, P = 0.050 and 2 days: +101 +/- 204%, P = 0.779) mRNA levels after SSC. It was concluded that fatiguing SSC exercise induces increased muscle BF during exercise, which is likely to be associated with pro-inflammatory processes in the exercised muscle.

Research paper thumbnail of Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk

The FASEB Journal, 2010

A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To pro... more A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To probe this linkage, we utilized rat models of low and high intrinsic aerobic endurance running capacity that differ also in the risk for metabolic syndrome. We investigated in skeletal muscle gene-phenotype relationships that connect aerobic endurance capacity with metabolic disease risk factors. The study compared 12 high capacity runners (HCRs) and 12 low capacity runners (LCRs) from generation 18 of selection that differed by 615% for maximal treadmill endurance running capacity. On average, LCRs were heavier and had increased blood glucose, insulin, and triglycerides compared with HCRs. HCRs were higher for resting metabolic rate, voluntary activity, serum high density lipoproteins, muscle capillarity, and mitochondrial area. Bioinformatic analysis of skeletal muscle gene expression data revealed that many genes up-regulated in HCRs were related to oxidative energy metabolism. Seven mean mRNA expression centroids, including oxidative phosphorylation and fatty acid metabolism, correlated significantly with several exercise capacity and disease risk phenotypes. These expression-phenotype correlations, together with diminished skeletal muscle capillarity and mitochondrial area in LCR rats, support the general hypothesis that an inherited intrinsic aerobic capacity can underlie disease risks.

Research paper thumbnail of Molecular adaptations of voltage-gated sodium ion channel related proteins after fatiguing stretch-shortening cycle exercise

Scandinavian journal of medicine & science in sports, 2008

Dystrophin associated protein alpha-syntrophin is known to interact with voltage-gated sodium ion... more Dystrophin associated protein alpha-syntrophin is known to interact with voltage-gated sodium ion channel (NaCh). Dystrophin is known to be sensitive to eccentric muscle actions. For this reason, the function of the NaChs might also be affected. Molecular adaptations of dystrophin, alpha-syntrophin and NaChs were investigated after fatiguing stretch-shortening cycle (SSC) exercise, which consisted of unilateral jumps on a sledge apparatus. Muscle biopsies were taken from the vastus lateralis muscle of eight healthy subjects immediately after (IA) and 2 days after (2D) the exercise to analyze mRNA levels and immunohistochemical staining patterns. SSC exercise resulted in decreased isometric maximal voluntary contraction (IA: -31+/-9%, 2D: -14+/-16%) and a delayed increase of plasma creatine kinase activity (2D: +178+/-211%). Despite muscle soreness (P<0.001), no morphological damage was observed and no changes were found in the mRNA concentrations. However, the relative changes of...

Research paper thumbnail of Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle

The FASEB Journal, 2006

Diabetes alters microvascular structure and function and is a major risk factor for cardiovascula... more Diabetes alters microvascular structure and function and is a major risk factor for cardiovascular diseases. In diabetic skeletal muscle, impaired angiogenesis and reduced VEGF-A expression have been observed, whereas in healthy muscle exercise is known to have opposite effects. We studied the effects of type 1 diabetes and combined exercise training on angiogenic mRNA expression and capillarization in mouse skeletal muscle. Microarray and real-time PCR analyses showed that diabetes altered the expression of several genes involved in angiogenesis. For example, levels of proangiogenic VEGF-A, VEGF-B, neuropilin-1, VEGFR-1, and VEGFR-2 were reduced and the levels of antiangiogenic thrombospondin-1 and retinoblastoma like-2 were increased. Exercise training alleviated some of these changes, but could not completely restore them. VEGF-A protein content was also reduced in diabetic muscles. In line with the reduced levels of VEGF-A and other angiogenic factors, and increased levels of angiogenesis inhibitors, capillary-to-muscle fiber ratio was lower in diabetic mice compared to healthy controls. Exercise training could not restore capillarization in diabetic mice. In conclusion, these data illustrate that type 1 diabetes is associated with reduced skeletal muscle capillarization and the dysregulation of complex angiogenesis pathways.-Kivelä, R., Silvennoinen, M., Touvra, A.-M., Lehti, T. M., Kainulainen, H., Vihko, V. Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle. FASEB J. 20, E921-E930 (2006) Key Words: angiogenesis ⅐ hyperglycemia ⅐ growth factor ⅐ VEGF E921 0892-6638/06/0020-0921 © FASEB E922 Vol. 20 June 2006 KIVELÄ ET AL. The FASEB Journal E923 DIABETES, EXERCISE TRAINING, AND ANGIOGENESIS Gene expressions are expressed in relation to the control group at the same time point. Statistically significant changes are color-coded: red ϭ up-regulated (two-based log of ratio (sample/control) Ն0.3 and PՅ0.0025), green ϭ down-regulated (two-based log of ratio (sample/control) Յ-0.3 and PՆ0.9975), yellow ϭ diabetes-induced change in expression was attenuated by exercise (significant change in expression in opposite direction in comparisons DT vs. D and D vs. C). Group abbreviations: D ϭ diabetic, DT ϭ diabetic trained, and T ϭ healthy trained, numbers ϭ time of the treatment in weeks.

Research paper thumbnail of CCBE1 Enhances Lymphangiogenesis via ADAMTS3-Mediated VEGF-C Activation

Research paper thumbnail of Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation

Research paper thumbnail of Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle

AJP: Heart and Circulatory Physiology, 2007

Blood and lymphatic vessels form together the circulatory system allowing the passage of fluids a... more Blood and lymphatic vessels form together the circulatory system allowing the passage of fluids and molecules within the body. Recently we showed that lymphatic capillaries are also found in the capillary bed of skeletal muscle. Exercise is known to induce angiogenesis in skeletal muscle, but it is not known whether exercise has effects on lymphangiogenesis or lymphangiogenic growth factors. We studied lymphatic vessel density and the expression of the main lymphangiogenic growth factors VEGF-C, VEGF-D, and their receptor VEGFR-3 in response to acute running exercise and endurance exercise training in the skeletal muscle of healthy and diabetic mice. VEGF-C mRNA expression increased after the acute exercise bout (P < 0.05) in healthy muscles, but there was no change in diabetic muscles. VEGF-C levels were not changed either in healthy or in diabetic muscle after the exercise training. Neither acute exercise nor exercise training had an effect on the mRNA expression of VEGF-D or VEGFR-3 in healthy or diabetic muscles. Lymphatic vessel density was similar in sedentary and trained mice and was more than 100-fold smaller than blood capillary density. Diabetes increased the mRNA expression of VEGF-D (P < 0.01).

Research paper thumbnail of Effects of streptozotocin-induced diabetes and physical training on gene expression of titin-based stretch-sensing complexes in mouse striated muscle

AJP: Endocrinology and Metabolism, 2006

Research paper thumbnail of Effects of exhaustive stretch-shortening cycle exercise on muscle blood flow during exercise

Acta Physiologica, 2006

The influence of exhaustive stretch-shortening cycle exercise (SSC) on skeletal muscle blood flow... more The influence of exhaustive stretch-shortening cycle exercise (SSC) on skeletal muscle blood flow (BF) during exercise is currently unknown. Quadriceps femoris (QF) BF was measured in eight healthy men using positron emission tomography before and 3 days after exhaustive SSC exercise. The SSC protocol consisted of maximal and submaximal drop jumps with one leg. Needle biopsies of the vastus lateralis muscles were taken immediately and 2 days after SSC for muscle endothelial nitric oxide synthase (eNOS) and interleukin-1-beta (IL-1beta) mRNA level determinations. All subjects reported subjective muscle soreness after SSC (P &amp;amp;amp;amp;lt; 0.001), which was well in line with a decrease in maximal isometric contraction force (MVC) and increase in serum creatine kinase activity (CK) (P = 0.018). After SSC muscle BF was 25% higher in entire QF (P = 0.043) and in its deep and superficial muscle regions, whereas oxygen uptake remained unchanged (P = 0.893). Muscle biopsies revealed increased IL-1beta (30 min: 152 +/- 75%, P = 0.012 and 2 days: 108 +/- 203%, P = 0.036) but decreased or unchanged eNOS (30 min; -21 +/- 57%, P = 0.050 and 2 days: +101 +/- 204%, P = 0.779) mRNA levels after SSC. It was concluded that fatiguing SSC exercise induces increased muscle BF during exercise, which is likely to be associated with pro-inflammatory processes in the exercised muscle.

Research paper thumbnail of Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk

The FASEB Journal, 2010

A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To pro... more A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To probe this linkage, we utilized rat models of low and high intrinsic aerobic endurance running capacity that differ also in the risk for metabolic syndrome. We investigated in skeletal muscle gene-phenotype relationships that connect aerobic endurance capacity with metabolic disease risk factors. The study compared 12 high capacity runners (HCRs) and 12 low capacity runners (LCRs) from generation 18 of selection that differed by 615% for maximal treadmill endurance running capacity. On average, LCRs were heavier and had increased blood glucose, insulin, and triglycerides compared with HCRs. HCRs were higher for resting metabolic rate, voluntary activity, serum high density lipoproteins, muscle capillarity, and mitochondrial area. Bioinformatic analysis of skeletal muscle gene expression data revealed that many genes up-regulated in HCRs were related to oxidative energy metabolism. Seven mean mRNA expression centroids, including oxidative phosphorylation and fatty acid metabolism, correlated significantly with several exercise capacity and disease risk phenotypes. These expression-phenotype correlations, together with diminished skeletal muscle capillarity and mitochondrial area in LCR rats, support the general hypothesis that an inherited intrinsic aerobic capacity can underlie disease risks.