Ellen Breen | University of California, San Diego (original) (raw)
Papers by Ellen Breen
European Respiratory Journal, 2001
This study investigates the effect of increased ventilation on the expression of messenger ribonu... more This study investigates the effect of increased ventilation on the expression of messenger ribonucleic acid (mRNA) levels of vascular endothelial growth factor (VEGF), basic ®broblast growth factor (bFGF) and transforming growth factorb 1 (TGF-b 1 ) in the diaphragm of intact, awake, spontaneously breathing rats, compared with responses in paralysed, mechanically-ventilated animals at similar blood gas and ventilatory levels.
AJP: Regulatory, Integrative and Comparative Physiology, 2009
High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat ... more High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat lungs. J. Appl. Physiol. 83(5): 1697-1705.-We hypothesized that wall stresses produced by high peak airway (Paw) and venous (Ppv) pressures would increase mRNA levels for structural proteins of the interstitial matrix in isolated rat lungs. Groups of lungs (n ϭ 6) were perfused for 4 h at a peak Paw of 35 cmH 2 O (HiPaw), cyclical peak Ppv of 28 cmH 2 O (HiPv), or baseline vascular and airway pressures (LoPress). In two separate groups, comparable peak pressures increased capillary filtration coefficient fourfold in each group. Northern blots were probed for mRNA of ␣ 1 (I), ␣ 1 (III), and ␣ 2 (IV) procollagen chains, laminin B chain, fibronectin, and transforming growth factor- 1 , and densities were normalized to 18S rRNA. mRNA was significantly higher in the HiPv group for type I (4.3-fold) and type III (3.8-fold) procollagen and laminin B chain (4.8-fold) and in the HiPaw group for type I (2.4-fold) and type IV (4.5-fold) procollagen and laminin B chain (2.3-fold) than in the LoPress group. Only fibronectin mRNA was significantly increased (3.9-fold) in the LoPress group relative to unperfused lungs. Estimated wall stresses were highest for alveolar septa in the HiPaw group and for capillaries in the HiPv group. The different patterns of mRNA expression are attributed to different regional stresses or extent of injury. collagen; fibrosis; pulmonary hypertension; barotrauma; fibronectin; vascular permeability
Environmental Health Perspectives, 2008
Journal of Applied Physiology, 2015
The ability to enhance muscle size and function is important for overall health. In this study, s... more The ability to enhance muscle size and function is important for overall health. In this study, skeletal myofiber vascular endothelial growth factor (VEGF) was hypothesized to regulate hypertrophy, capillarity and contractile function in response to functional overload (FO). Adult myofiber-specific VEGF gene ablated mice (skmVEGF(-/-)) and wild type (WT) littermates underwent plantaris FO or sham surgery (SHAM). Mass, morphology, in vivo function, IGF-1, bFGF, HGF and Akt were measured at 7, 14 and 30 days. FO resulted in hypertrophy in both genotypes, but fiber sizes were 13% and 23% smaller after 14 and 30 days, respectively, and mass 15% less after 30 days in skmVEGF(-/-) than WT. FO increased isometric force after 30 days in WT and decreased in skmVEGF(-/-) after 7 and 14 days. FO also resulted in a reduction in specific force and this differed between genotypes at 14 days. Fatigue resistance improved only in 14-day WT mice. Capillary density was decreased by FO in both genotypes. However capillary to fiber ratios were 19% and 15% lower in skmVEGF(-/-) than WT at the 14- and 30-day time points, respectively. IGF-1 was increased by FO at all time points and was 45% and 40% greater in skmVEGF(-/-) than WT after 7 and 14 days, respectively. bFGF, HGF, total Akt and phospho-Akt, independent of VEGF expression, and VEGF levels in WT were increased after 7 days of FO. These findings suggest VEGF-dependent capillary maintenance supports muscle growth and function in overloaded muscle and is not rescued by compensatory IGF-1 expression.
Textbook of Pulmonary Vascular Disease, 2010
Mutagenesis is a change or alteration in the DNA sequences of a gene. Mutagenic events may occur ... more Mutagenesis is a change or alteration in the DNA sequences of a gene. Mutagenic events may occur spontaneously within the genome of an organism and many times do not lead to functional consequences or an altered phenotype. However, at times a change in the coding sequence of a gene manifests itself as a dysfunctional phenotypic trait or predisposes an individual to a particular disease. The human genome may contain variations or mutations in an individual or in a related group of individuals that predispose them to a particular disease. Identifying and understanding these mutations (or polymorphisms) in gene structure can aid in the understanding, diagnosis, and treatment of patients. Quite the opposite to the mutations that spontaneously occur and may be difficult to identify, purposefully introducing mutations into a candidate gene that is then expressed in a cell or mouse model systems can readily reveal important information. This chapter provides an overview of the strategy to clone a gene, express it in a cultured cell system, and elucidate the function of the expressed gene product using mutagenesis methods. The value of this type of experimental approach will be highlighted by reviewing two pulmonary genes that have been analyzed using in vitro mutagenesis methods, the potassium channel Kv1.5 and the bone morphogenetic protein receptor II.
D33. AIRWAY INFECTION: MICROBIOME AND MECHANISMS, 2010
Journal of Cellular Biochemistry, 2007
Vascular endothelial growth factor
Environmental Health Perspectives, 2008
Journal of Applied Physiology
Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chr... more Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. We sought to determine the effect of chronic hypoxia (8 wk, inspired O2 fraction = 0.12) on skeletal muscle gene expression of VEGF, its receptors (flt-1 and flk-1), basic fibroblast growth factor, and transforming growth factor-beta1. Wistar rats were exposed to chronic hypoxia (n = 12) or room air (n = 12). After the exposure period, six animals from each group were subjected to a single 1-h treadmill exercise bout (18 m/min on a 10 degrees incline) in room air while the remaining six animals served as rest controls. Morphological analysis revealed that chronic hypoxia did not increase skeletal muscle capillarity. Northern blot analyses showed that chronic hypoxia decreased resting VEGF, flt-1, and flk-1 mRNA by 23, 68, and 42%, respectively (P < 0.05). The VEGF mRNA response to exercise was also decreased (4.1- and 2.7-fold increase in room air and chronic hypoxia, respectively, P < 0.05). In contrast, neither transforming growth factor-beta1 nor basic fibroblast growth factor mRNA was significantly altered by chronic hypoxia. In conclusion, prolonged exposure to hypoxia attenuated gene expression of VEGF and its receptors flt-1 and flk-1 in rat gastrocnemius muscle. These findings may provide an explanation for the lack of mammalian skeletal muscle angiogenesis that is observed after chronic hypoxia.
Journal of Applied Physiology
Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chr... more Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. We sought to determine the effect of chronic hypoxia (8 wk, inspired O2 fraction = 0.12) on skeletal muscle gene expression of VEGF, its receptors (flt-1 and flk-1), basic fibroblast growth factor, and transforming growth factor-beta1. Wistar rats were exposed to chronic hypoxia (n = 12) or room air (n = 12). After the exposure period, six animals from each group were subjected to a single 1-h treadmill exercise bout (18 m/min on a 10 degrees incline) in room air while the remaining six animals served as rest controls. Morphological analysis revealed that chronic hypoxia did not increase skeletal muscle capillarity. Northern blot analyses showed that chronic hypoxia decreased resting VEGF, flt-1, and flk-1 mRNA by 23, 68, and 42%, respectively (P < 0.05). The VEGF mRNA response to exercise was also decreased (4.1- and 2.7-fold increase in room air and chronic hypoxia, respectively, P < 0.05). In contrast, neither transforming growth factor-beta1 nor basic fibroblast growth factor mRNA was significantly altered by chronic hypoxia. In conclusion, prolonged exposure to hypoxia attenuated gene expression of VEGF and its receptors flt-1 and flk-1 in rat gastrocnemius muscle. These findings may provide an explanation for the lack of mammalian skeletal muscle angiogenesis that is observed after chronic hypoxia.
Journal of Applied Physiology
Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transform... more Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transforming growth factor-beta(1) (TGF-beta(1)) and basic fibroblast growth factor (bFGF), has been found to increase in rat skeletal muscle after a single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response to exercise, which suggests that, if VEGF is important in muscle angiogenesis, hypoxic training might produce greater capillary growth than normoxic training. Therefore, we examined the effects of exercise training (treadmill running at the same absolute intensity) in normoxia and hypoxia (inspired O(2) fraction = 0.12) on rat skeletal muscle capillarity and on resting and postexercise gene expression of VEGF, its major receptors (flt-1 and flk-1), TGF-beta(1), and bFGF. Normoxic training did not alter basal or exercise-induced VEGF mRNA levels but produced a modest twofold increase in bFGF mRNA (P < 0.05). Rats trained in hypoxia exhibited an attenuated VEGF mRNA response to exercise (1.8-fold compared 3.4-fold with normoxic training; P < 0.05), absent TGF-beta(1) and flt-1 mRNA responses to exercise, and an approximately threefold (P < 0.05) decrease in bFGF mRNA levels. flk-1 mRNA levels were not significantly altered by either normoxic or hypoxic training. An increase in skeletal muscle capillarity was observed only in hypoxically trained rats. These data show that, whereas training in hypoxia potentiates the adaptive angiogenic response of skeletal muscle to a given absolute intensity of exercise, this was not evident in the gene expression of VEGF or its receptors when assessed at the end of training.
Mechanical tension extending throughout the structural elements of the lung is a potential stimul... more Mechanical tension extending throughout the structural elements of the lung is a potential stimulus for cell proliferation and gene expression. Pulmonary fibroblasts located in the interstitial space of the capillary wall throughout the lung parenchyma and within the large vessels and airways are uniquely situated to sense changes in mechanical force. Therefore, we used the polymerase chain reaction-based method of
A19. IMAGING THE DISTAL LUNG: ADVANCES IN TECHNIQUE AND APPLICATION, 2009
Journal of cellular physiology, Jan 22, 2015
Exercise is dependent on adequate oxygen supply for mitochondrial respiration in both cardiac and... more Exercise is dependent on adequate oxygen supply for mitochondrial respiration in both cardiac and locomotor muscle. To determine whether skeletal myofiber VEGF is critical for regulating exercise capacity, independent of VEGF function in the heart, ablation of the VEGF gene was targeted to skeletal myofibers (skmVEGF-/-) during embryogenesis (∼ E9.5), leaving intact VEGF expression by all other cells in muscle. In adult mice, VEGF levels were decreased in the soleus (by 65%), plantaris (94%), gastrocnemius (74%), EDL (99%) and diaphragm (64%) (p < 0.0001, each muscle). VEGF levels were unchanged in the heart. Treadmill speed (WT 86 ± 4 cm/sec., skmVEGF-/- 70 ± 5 cm/sec., p = 0.006) and endurance (WT 78 ± 24 min., skmVEGF-/- 18 ± 4 min., p = 0.0004) were severely limited in skmVEGF-/- mice in contrast to minor effect of conditional skmVEGF gene deletion in the adult. Body weight was also reduced (WT 22.8 ± 1.6 g, skmVEGF-/-, 21.1 ± 1.5, p = 0.02), but the muscle mass/body weight ...
Journal of applied physiology (Bethesda, Md. : 1985), 2000
Acute exercise increases vascular endothelial growth factor (VEGF), transforming growth factor-be... more Acute exercise increases vascular endothelial growth factor (VEGF), transforming growth factor-beta(1) (TGF-beta(1)), and basic fibroblast growth factor (bFGF) mRNA levels in skeletal muscle, with the greatest increase in VEGF mRNA. VEGF functions via binding to the VEGF receptors Flk-1 and Flt-1. Captopril, an angiotensin-converting enzyme inhibitor, has been suggested to reduce the microvasculature in resting and exercising skeletal muscle. However, the molecular mechanisms responsible for this reduction have not been investigated. We hypothesized that this might occur via reduced VEGF, TGF-beta(1), bFGF, Flk-1, and Flt-1 gene expression at rest and after exercise. To investigate this, 10-wk-old female Wistar rats were placed into four groups (n = 6 each): 1) saline + rest; 2) saline + exercise; 3) 100 mg/kg ip captopril + rest; and 4) 100 mg/kg ip captopril + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10 degrees incline. VEGF, TGF-beta(1), bFGF, Flk-1, and Fl...
Journal of applied physiology (Bethesda, Md. : 1985), 1997
Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., m... more Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for alpha1(III) and alpha2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-beta1. In contrast, alph...
Journal of applied physiology (Bethesda, Md. : 1985), Jan 15, 2014
While it is well recognized that pulmonary deposition of inhaled particles is lowered in microgra... more While it is well recognized that pulmonary deposition of inhaled particles is lowered in microgravity (μG) compared with gravity on the ground (1G), the absence of sedimentation causes fine particles to penetrate deeper in the lung in μG. Using quantitative magnetic resonance imaging (MRI), we determined the effect of gravity on peripheral deposition (DEPperipheral) of fine particles. Aerosolized 0.95-μm-diameter ferric oxide particles were delivered to spontaneously breathing rats placed in plethysmographic chambers both in μG aboard the NASA Microgravity Research Aircraft and at 1G. Following exposure, lungs were perfusion fixed, fluid filled, and imaged in a 3T MR scanner. The MR signal decay rate, R2*, was measured in each voxel of the left lung from which particle deposition (DEP) was determined based on a calibration curve. Regional deposition was assessed by comparing DEP between the outer (DEPperipheral) and inner (DEPcentral) areas on each slice, and expressed as the centra...
A108. HOW USEFUL ARE ANIMAL MODELS OF LUNG DISEASE?, 2011
European Respiratory Journal, 2001
This study investigates the effect of increased ventilation on the expression of messenger ribonu... more This study investigates the effect of increased ventilation on the expression of messenger ribonucleic acid (mRNA) levels of vascular endothelial growth factor (VEGF), basic ®broblast growth factor (bFGF) and transforming growth factorb 1 (TGF-b 1 ) in the diaphragm of intact, awake, spontaneously breathing rats, compared with responses in paralysed, mechanically-ventilated animals at similar blood gas and ventilatory levels.
AJP: Regulatory, Integrative and Comparative Physiology, 2009
High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat ... more High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat lungs. J. Appl. Physiol. 83(5): 1697-1705.-We hypothesized that wall stresses produced by high peak airway (Paw) and venous (Ppv) pressures would increase mRNA levels for structural proteins of the interstitial matrix in isolated rat lungs. Groups of lungs (n ϭ 6) were perfused for 4 h at a peak Paw of 35 cmH 2 O (HiPaw), cyclical peak Ppv of 28 cmH 2 O (HiPv), or baseline vascular and airway pressures (LoPress). In two separate groups, comparable peak pressures increased capillary filtration coefficient fourfold in each group. Northern blots were probed for mRNA of ␣ 1 (I), ␣ 1 (III), and ␣ 2 (IV) procollagen chains, laminin B chain, fibronectin, and transforming growth factor- 1 , and densities were normalized to 18S rRNA. mRNA was significantly higher in the HiPv group for type I (4.3-fold) and type III (3.8-fold) procollagen and laminin B chain (4.8-fold) and in the HiPaw group for type I (2.4-fold) and type IV (4.5-fold) procollagen and laminin B chain (2.3-fold) than in the LoPress group. Only fibronectin mRNA was significantly increased (3.9-fold) in the LoPress group relative to unperfused lungs. Estimated wall stresses were highest for alveolar septa in the HiPaw group and for capillaries in the HiPv group. The different patterns of mRNA expression are attributed to different regional stresses or extent of injury. collagen; fibrosis; pulmonary hypertension; barotrauma; fibronectin; vascular permeability
Environmental Health Perspectives, 2008
Journal of Applied Physiology, 2015
The ability to enhance muscle size and function is important for overall health. In this study, s... more The ability to enhance muscle size and function is important for overall health. In this study, skeletal myofiber vascular endothelial growth factor (VEGF) was hypothesized to regulate hypertrophy, capillarity and contractile function in response to functional overload (FO). Adult myofiber-specific VEGF gene ablated mice (skmVEGF(-/-)) and wild type (WT) littermates underwent plantaris FO or sham surgery (SHAM). Mass, morphology, in vivo function, IGF-1, bFGF, HGF and Akt were measured at 7, 14 and 30 days. FO resulted in hypertrophy in both genotypes, but fiber sizes were 13% and 23% smaller after 14 and 30 days, respectively, and mass 15% less after 30 days in skmVEGF(-/-) than WT. FO increased isometric force after 30 days in WT and decreased in skmVEGF(-/-) after 7 and 14 days. FO also resulted in a reduction in specific force and this differed between genotypes at 14 days. Fatigue resistance improved only in 14-day WT mice. Capillary density was decreased by FO in both genotypes. However capillary to fiber ratios were 19% and 15% lower in skmVEGF(-/-) than WT at the 14- and 30-day time points, respectively. IGF-1 was increased by FO at all time points and was 45% and 40% greater in skmVEGF(-/-) than WT after 7 and 14 days, respectively. bFGF, HGF, total Akt and phospho-Akt, independent of VEGF expression, and VEGF levels in WT were increased after 7 days of FO. These findings suggest VEGF-dependent capillary maintenance supports muscle growth and function in overloaded muscle and is not rescued by compensatory IGF-1 expression.
Textbook of Pulmonary Vascular Disease, 2010
Mutagenesis is a change or alteration in the DNA sequences of a gene. Mutagenic events may occur ... more Mutagenesis is a change or alteration in the DNA sequences of a gene. Mutagenic events may occur spontaneously within the genome of an organism and many times do not lead to functional consequences or an altered phenotype. However, at times a change in the coding sequence of a gene manifests itself as a dysfunctional phenotypic trait or predisposes an individual to a particular disease. The human genome may contain variations or mutations in an individual or in a related group of individuals that predispose them to a particular disease. Identifying and understanding these mutations (or polymorphisms) in gene structure can aid in the understanding, diagnosis, and treatment of patients. Quite the opposite to the mutations that spontaneously occur and may be difficult to identify, purposefully introducing mutations into a candidate gene that is then expressed in a cell or mouse model systems can readily reveal important information. This chapter provides an overview of the strategy to clone a gene, express it in a cultured cell system, and elucidate the function of the expressed gene product using mutagenesis methods. The value of this type of experimental approach will be highlighted by reviewing two pulmonary genes that have been analyzed using in vitro mutagenesis methods, the potassium channel Kv1.5 and the bone morphogenetic protein receptor II.
D33. AIRWAY INFECTION: MICROBIOME AND MECHANISMS, 2010
Journal of Cellular Biochemistry, 2007
Vascular endothelial growth factor
Environmental Health Perspectives, 2008
Journal of Applied Physiology
Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chr... more Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. We sought to determine the effect of chronic hypoxia (8 wk, inspired O2 fraction = 0.12) on skeletal muscle gene expression of VEGF, its receptors (flt-1 and flk-1), basic fibroblast growth factor, and transforming growth factor-beta1. Wistar rats were exposed to chronic hypoxia (n = 12) or room air (n = 12). After the exposure period, six animals from each group were subjected to a single 1-h treadmill exercise bout (18 m/min on a 10 degrees incline) in room air while the remaining six animals served as rest controls. Morphological analysis revealed that chronic hypoxia did not increase skeletal muscle capillarity. Northern blot analyses showed that chronic hypoxia decreased resting VEGF, flt-1, and flk-1 mRNA by 23, 68, and 42%, respectively (P < 0.05). The VEGF mRNA response to exercise was also decreased (4.1- and 2.7-fold increase in room air and chronic hypoxia, respectively, P < 0.05). In contrast, neither transforming growth factor-beta1 nor basic fibroblast growth factor mRNA was significantly altered by chronic hypoxia. In conclusion, prolonged exposure to hypoxia attenuated gene expression of VEGF and its receptors flt-1 and flk-1 in rat gastrocnemius muscle. These findings may provide an explanation for the lack of mammalian skeletal muscle angiogenesis that is observed after chronic hypoxia.
Journal of Applied Physiology
Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chr... more Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. We sought to determine the effect of chronic hypoxia (8 wk, inspired O2 fraction = 0.12) on skeletal muscle gene expression of VEGF, its receptors (flt-1 and flk-1), basic fibroblast growth factor, and transforming growth factor-beta1. Wistar rats were exposed to chronic hypoxia (n = 12) or room air (n = 12). After the exposure period, six animals from each group were subjected to a single 1-h treadmill exercise bout (18 m/min on a 10 degrees incline) in room air while the remaining six animals served as rest controls. Morphological analysis revealed that chronic hypoxia did not increase skeletal muscle capillarity. Northern blot analyses showed that chronic hypoxia decreased resting VEGF, flt-1, and flk-1 mRNA by 23, 68, and 42%, respectively (P < 0.05). The VEGF mRNA response to exercise was also decreased (4.1- and 2.7-fold increase in room air and chronic hypoxia, respectively, P < 0.05). In contrast, neither transforming growth factor-beta1 nor basic fibroblast growth factor mRNA was significantly altered by chronic hypoxia. In conclusion, prolonged exposure to hypoxia attenuated gene expression of VEGF and its receptors flt-1 and flk-1 in rat gastrocnemius muscle. These findings may provide an explanation for the lack of mammalian skeletal muscle angiogenesis that is observed after chronic hypoxia.
Journal of Applied Physiology
Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transform... more Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transforming growth factor-beta(1) (TGF-beta(1)) and basic fibroblast growth factor (bFGF), has been found to increase in rat skeletal muscle after a single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response to exercise, which suggests that, if VEGF is important in muscle angiogenesis, hypoxic training might produce greater capillary growth than normoxic training. Therefore, we examined the effects of exercise training (treadmill running at the same absolute intensity) in normoxia and hypoxia (inspired O(2) fraction = 0.12) on rat skeletal muscle capillarity and on resting and postexercise gene expression of VEGF, its major receptors (flt-1 and flk-1), TGF-beta(1), and bFGF. Normoxic training did not alter basal or exercise-induced VEGF mRNA levels but produced a modest twofold increase in bFGF mRNA (P < 0.05). Rats trained in hypoxia exhibited an attenuated VEGF mRNA response to exercise (1.8-fold compared 3.4-fold with normoxic training; P < 0.05), absent TGF-beta(1) and flt-1 mRNA responses to exercise, and an approximately threefold (P < 0.05) decrease in bFGF mRNA levels. flk-1 mRNA levels were not significantly altered by either normoxic or hypoxic training. An increase in skeletal muscle capillarity was observed only in hypoxically trained rats. These data show that, whereas training in hypoxia potentiates the adaptive angiogenic response of skeletal muscle to a given absolute intensity of exercise, this was not evident in the gene expression of VEGF or its receptors when assessed at the end of training.
Mechanical tension extending throughout the structural elements of the lung is a potential stimul... more Mechanical tension extending throughout the structural elements of the lung is a potential stimulus for cell proliferation and gene expression. Pulmonary fibroblasts located in the interstitial space of the capillary wall throughout the lung parenchyma and within the large vessels and airways are uniquely situated to sense changes in mechanical force. Therefore, we used the polymerase chain reaction-based method of
A19. IMAGING THE DISTAL LUNG: ADVANCES IN TECHNIQUE AND APPLICATION, 2009
Journal of cellular physiology, Jan 22, 2015
Exercise is dependent on adequate oxygen supply for mitochondrial respiration in both cardiac and... more Exercise is dependent on adequate oxygen supply for mitochondrial respiration in both cardiac and locomotor muscle. To determine whether skeletal myofiber VEGF is critical for regulating exercise capacity, independent of VEGF function in the heart, ablation of the VEGF gene was targeted to skeletal myofibers (skmVEGF-/-) during embryogenesis (∼ E9.5), leaving intact VEGF expression by all other cells in muscle. In adult mice, VEGF levels were decreased in the soleus (by 65%), plantaris (94%), gastrocnemius (74%), EDL (99%) and diaphragm (64%) (p < 0.0001, each muscle). VEGF levels were unchanged in the heart. Treadmill speed (WT 86 ± 4 cm/sec., skmVEGF-/- 70 ± 5 cm/sec., p = 0.006) and endurance (WT 78 ± 24 min., skmVEGF-/- 18 ± 4 min., p = 0.0004) were severely limited in skmVEGF-/- mice in contrast to minor effect of conditional skmVEGF gene deletion in the adult. Body weight was also reduced (WT 22.8 ± 1.6 g, skmVEGF-/-, 21.1 ± 1.5, p = 0.02), but the muscle mass/body weight ...
Journal of applied physiology (Bethesda, Md. : 1985), 2000
Acute exercise increases vascular endothelial growth factor (VEGF), transforming growth factor-be... more Acute exercise increases vascular endothelial growth factor (VEGF), transforming growth factor-beta(1) (TGF-beta(1)), and basic fibroblast growth factor (bFGF) mRNA levels in skeletal muscle, with the greatest increase in VEGF mRNA. VEGF functions via binding to the VEGF receptors Flk-1 and Flt-1. Captopril, an angiotensin-converting enzyme inhibitor, has been suggested to reduce the microvasculature in resting and exercising skeletal muscle. However, the molecular mechanisms responsible for this reduction have not been investigated. We hypothesized that this might occur via reduced VEGF, TGF-beta(1), bFGF, Flk-1, and Flt-1 gene expression at rest and after exercise. To investigate this, 10-wk-old female Wistar rats were placed into four groups (n = 6 each): 1) saline + rest; 2) saline + exercise; 3) 100 mg/kg ip captopril + rest; and 4) 100 mg/kg ip captopril + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10 degrees incline. VEGF, TGF-beta(1), bFGF, Flk-1, and Fl...
Journal of applied physiology (Bethesda, Md. : 1985), 1997
Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., m... more Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for alpha1(III) and alpha2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-beta1. In contrast, alph...
Journal of applied physiology (Bethesda, Md. : 1985), Jan 15, 2014
While it is well recognized that pulmonary deposition of inhaled particles is lowered in microgra... more While it is well recognized that pulmonary deposition of inhaled particles is lowered in microgravity (μG) compared with gravity on the ground (1G), the absence of sedimentation causes fine particles to penetrate deeper in the lung in μG. Using quantitative magnetic resonance imaging (MRI), we determined the effect of gravity on peripheral deposition (DEPperipheral) of fine particles. Aerosolized 0.95-μm-diameter ferric oxide particles were delivered to spontaneously breathing rats placed in plethysmographic chambers both in μG aboard the NASA Microgravity Research Aircraft and at 1G. Following exposure, lungs were perfusion fixed, fluid filled, and imaged in a 3T MR scanner. The MR signal decay rate, R2*, was measured in each voxel of the left lung from which particle deposition (DEP) was determined based on a calibration curve. Regional deposition was assessed by comparing DEP between the outer (DEPperipheral) and inner (DEPcentral) areas on each slice, and expressed as the centra...
A108. HOW USEFUL ARE ANIMAL MODELS OF LUNG DISEASE?, 2011