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At least 541 records · Page 30

Dynamic Foot Stimulation Attenuates Soleus Muscle Atrophy Induced by Hindlimb Unloading in Rats

Unloading-induced myofiber atrophy is a phenomenon that occurs in the aging population, bed-ridden patients and astronauts. The objective of this study was to determine whether or not dynamic foot stimulation (DFS) applied to the plantar surface of the rat foot can serve as a countermeasure to the soleus muscle atrophy normally observed in hindlimb unloaded (HU) rats. Thirty mature adult (6-month-old) male Wistar rats were randomly assigned into ambulatory control (AMB), hindlimb unloaded alone (HU), or hindlimb unloaded with the application of DFS (HU+DFS) groups. A dynamic pattern of pressure was applied to the right foot of each HU animal using a specially fabricated boot containing an inflatable air bladder connected to a solenoid air pump controlled by a laptop computer. The anti-atrophic effects of DFS were quantified morphometrically in frozen cross-sections of soleus muscle stained using the metachromatic-ATPase fiber typing technique. Application of DFS during HU significantly counteracted the atrophic response observed in the soleus by preventing approximately 85% of the reduction in Type I myofiber cross-sectional area (CSA) observed during HU. However, DFS did not protect type II fibers of the soleus from HU-induced atrophy or any fiber type in the soleus muscle of the contralateral control leg of the DFS-treated HU animals. These results illustrate that the application of DFS to the rat foot is an effective countermeasure to soleus muscle atrophy induced by HU.

Kyparos, Antonios↗

Inadequate Loading Stimulus on ISS Results in Bone and Muscle Loss

INTRODUCTION Exercise has been the primary countermeasure to combat musculoskeletal changes during International Space Station (ISS) missions. However, these countermeasures have not been successful in preventing loss of bone mineral density (BMD) or muscle volume in crew members. METHODS We examined lower extremity loading during typical days on-orbit and on Earth for four ISS crew members. In-shoe forces were monitored using force-measuring insoles placed inside the shoes. BMD (by DXA), muscle volumes (by MRI), and strength were measured before and after long-duration spaceflight (181 +/- 15 days). RESULTS The peak forces measured during ISS activity were significantly less than those measured in 1g for the same activities. Typical single-leg loads on-orbit during walking and running were 0.89 +/- 0.17 body weights (BW) and 1.28 +/- 0.18 BW compared to 1.18 +/- 0.11 BW and 2.36 +/- .22 BW in 1g, respectively [2]. Crew members were only loaded for an average of 43.17 +/- 14.96 min a day while performing exercise on-orbit even though 146.8 min were assigned for exercise each day. Areal BMD decreased in the femoral neck and total hip by 0.71 +/- 0.34% and 0.81 +/- 0.21% per month, respectively. Changes in muscle volume were observed in the lower extremity (-10 to -16% calf; -4 to -7% thigh) but there were no changes in the upper extremity (+0.4 to -0.8%). Decrements in isometric and isokinetic strength at the knee (range: -10.4 to -24.1%), ankle (range: -4 to -22.3%), and elbow (range: -7.5 to - 16.7%) were also observed. Knee extension endurance tests showed an overall decline in total work (-14%) but an increased resistance to fatigue post-flight. DISCUSSION AND CONCLUSIONS Our findings support the conclusion that the measured exercise durations and/or loading stimuli were insufficient to protect bone and muscle health.

Rice, A. J.↗

Estimated Muscle Loads During Squat Exercise in Microgravity Conditions

Loss of muscle mass in microgravity is one of the primary factors limiting long-term space flight. NASA researchers have developed a number of exercise devices to address this problem. The most recent is the Advanced Resistive Exercise Device (ARED), which is currently used by astronauts on the International Space Station (ISS) to emulate typical free-weight exercises in microgravity. ARED exercise on the ISS is intended to reproduce Earth-level muscle loads, but the actual muscle loads produced remain unknown as they cannot currently be measured directly. In this study we estimated muscle loads experienced during squat exercise on ARED in microgravity conditions representative of Mars, the moon, and the ISS. The estimates were generated using a subject-specific musculoskeletal computer model and ARED exercise data collected on Earth. The results provide insight into the capabilities and limitations of the ARED machine.

Fregly, Christopher D.↗

Integrated Resistance and Aerobic Training Maintains Cardiovascular and Skeletal Muscle Fitness During 14 Days of Bed Rest

Background: Known incompatibilities exist between resistance and aerobic training. Of particular importance are findings that concurrent resistance and aerobic training reduces the effectiveness of the resistance training and limits skeletal muscle adaptations (example: Dudley & Djamil, 1985). Numerous unloading studies have documented the effectiveness of resistance training alone for the maintenance of skeletal muscle size and strength. However the practical applications of those studies are limited because long ]duration crew members perform both aerobic and resistance exercise throughout missions/spaceflight. To date, such integrated training on the International Space Station (ISS) has not been fully effective in the maintenance of skeletal muscle function. Purpose: The purpose of this study was to evaluate the efficacy of high intensity concurrent resistance and aerobic training for the maintenance of cardiovascular fitness and skeletal muscle strength, power and endurance over 14 days of strict bed rest. Methods: 9 subjects (8 male and 1 female; 34.5 +/- 8.2 years) underwent 14 days of bed rest with concurrent training. Resistance and aerobic training were integrated as shown in table 1. Days that included 2 exercise sessions had a 4-8 hour rest between exercise bouts. The resistance training consisted of 3 sets of 12 repetitions of squat, heel raise, leg press and hamstring curl exercise. Aerobic exercise consisted of periodized interval training that included 30 sec, 2 min and 4 min intervals alternating by day with continuous aerobic exercise.

Ploutz-Snyder, Lori↗

Implicit Formulation of Muscle Dynamics in OpenSim

Astronauts lose bone and muscle mass during spaceflight. Exercise countermeasure is the primary method for counteracting bone and muscle mass loss in space. New spacecraft exercise device concepts are currently being developed for the NASAs new crew exploration vehicle. The NASA Digital Astronaut Project (DAP) uses computational modeling to help determine if the new exercise devices will be effective as countermeasures. The NASA Digital Astronaut Project is developing the ability to utilize predictive simulation to provide insight into the change in kinematics and kinetics with a change in device and gravitational environment (1-g versus 0-g). For example, in space exercise the subject's body weight is applied in addition to the loads prescribed for musculoskeletal maintenance. How and where these loads are applied obviously directly impacts bone and tissue loads. Additionally, due to space vehicle structural requirements, exercise devices are often placed on vibration isolation systems. This changes the apparent impedance or stiffness of the device as seen by the user. Data collection under these conditions is often impractical and limited. Predictive modeling provides a means to have a virtual subject to test hypotheses. Predictive simulation provides a virtual subject for which we are able to perform studies such as sensitivity to device loading and vibration isolation without the need for laboratory kinematic or kinetic test data.Direct Collocation optimization provides an efficient means to perform task based optimization and predictive modeling. It is relatively straight forward to structure a physical exercise task in a Direct Collocation mathematical formulation: perform a motion such that you start at an initial pose, achieve a given amount of deflection i.e a squat, return to the initial pose, and minimize muscle activation cost. Direct Collocation is advantageous in that it does not require numerical integration to evaluate the objective function. Instead, the system dynamics are transformed to discrete time and the optimizer is constrained such that the solution is not considered to be a valid unless the dynamic equations are satisfied at all time points. The simulation and optimization are effectively done simultaneously. Due to the implicit integration, time steps can be more coarse than in a differential equation solver. In a gait scenario this means that that the model constraints and cost function are evaluated at 100 nodes in the gait cycle versus 10,000 integration steps in a variable-step forward dynamic simulation. Furthermore, no time is wasted on accurate simulations of movements that are far from the optimum. Constrained optimization algorithms require a Jacobian matrix that contains the partial derivatives of each of the dynamic constraints with respect to of each of the state and control variables at all time points. This is a large but sparse matrix. An implicit dynamics formulation requires computation of the dynamic residuals f as a function of the states x and their derivatives, and controls u:f(x, dxdt, u) 0If the dynamics of musculoskeletal system are formulated implicitly, the Jacobian elements are often available analytically, eliminating the need for numerical differentiation; this is obviously computationally advantageous. Additionally, implicit formulation of musculoskeletal dynamics do not suffer from singularities from low mass bodies, zero muscle activation, or other stiff system or

physical exercise↗

The Mega-MUSCLES Treasury Survey: X-Ray to Infrared Spectral Energy Distributions of a Representative Sample of M Dwarfs

We present 5–1 × 107 Å spectral energy distributions (SEDs) for 12 M dwarf stars covering spectral types M0–M8. Our SEDs are provided for community use as a sequel to the Measurements of the Ultraviolet Spectral Characteristics of Low-mass Exoplanetary Systems (MUSCLES) survey. The 12 stars include eight known exoplanet hosts and four stars chosen to fill out key parameter space in spectral type and rotation period. The SEDs are constructed from Hubble Space Telescope ultraviolet spectroscopy and XMM Newton, Chandra, and/or Swift X-ray observations, and completed with various model data, including Lyα reconstructions, PHOENIX optical models, APEC coronal models, and differential emission measure models in the currently-unobservable extreme ultraviolet. We provide a complete overview of the Mega-MUSCLES program, including a description of the observations, models, and SED construction. The SEDs are available as MAST high-level science products and we describe the various data products here. We also present ensemble measurements from our sample that are of particular relevance to exoplanet science, including the high-energy fluxes in the habitable zone and the farultraviolet to near-ultraviolet ratio. Combined with MUSCLES, Mega-MUSCLES provides SEDs covering a wide range of M dwarf spectral types and ages such that suitable proxies for any M dwarf planet host of interest may be found in our sample. However, we find that ultraviolet and X-ray fluxes can vary even between stars with similar parameters, such that observations of each exoplanet host star will remain the gold standard for interpreting exoplanet atmosphere observations.

David J. Wilson↗

Effects of regular exercise training on skeletal muscle contractile function

Skeletal muscle function is critical to movement and one's ability to perform daily tasks, such as eating and walking. One objective of this article is to review the contractile properties of fast and slow skeletal muscle and single fibers, with particular emphasis on the cellular events that control or rate limit the important mechanical properties. Another important goal of this article is to present the current understanding of how the contractile properties of limb skeletal muscle adapt to programs of regular exercise.

NASA Discipline Musculoskeletal↗

Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms

The goal of this article is to examine our current understanding of the chain of events known to be involved in the adaptive process whereby specific genes and their protein products undergo altered expression; specifically, skeletal muscle adaptation in response to altered loading states will be discussed, with a special focus on the regulation of the contractile protein, myosin heavy chain gene expression. This protein, which is both an important structural and regulatory protein comprising the contractile apparatus, can be expressed as different isoforms, thereby having an impact on the functional diversity of the muscle. Because the regulation of the myosin gene family is under the control of a complex set of processes including, but not limited to, activity, hormonal, and metabolic factors, this protein will serve as a cellular "marker" for studies of muscle plasticity in response to various mechanical perturbations in which the quantity and type of myosin isoform, along with other important cellular proteins, are altered in expression.

Non-NASA Center↗

Energetics of muscle contraction: the whole is less than the sum of its parts

Understanding muscle energetics is a problem in optimizing supply of ATP to the demands of ATPases. The complexity of reactions and their fluxes to achieve this balance is greatly reduced by recognizing constraints imposed by the integration of common metabolites at fixed stoichiometry among modular units. ATPase is driven externally. Oxidative phosphorylation and glycogenolysis are the suppliers. We focus on their regulation which involves different controls, but reduces to two principles that enable facile experimental analysis of the supply and demand fluxes. The ratio of concentration of phosphocreatine (PCr) to ATP, not their individual values, sets the range of achievable concentrations of ADP in resting and active muscle (at fixed pH) in different cell types. This principle defines the fraction of available flux of oxidative phosphorylation utilized (at fixed enzyme activities). Then the kinetics of PCr recovery defines the kinetics of oxygen supply and substrate utilization. The second principle is the constancy of PCr and H(+) (lactate) production by glycogenolysis due to the coupling of ATPase and glycolysis. This principle enables glycogenolytic flux to be measured from intracellular proton loads. Further simplification occurs because the magnitude of the interacting fluxes and metabolite concentrations are specified within narrow limits when both the resting and active fluxes are quantified. Thus there is a small set of rules for assessing and understanding the thermodynamics and kinetics of muscle energetics.

NASA Program Biomedical Research and Countermeasur↗

Protein machines and self assembly in muscle organization

The remarkable order of striated muscle is the result of a complex series of protein interactions at different levels of organization. Within muscle, the thick filament and its major protein myosin are classical examples of functioning protein machines. Our understanding of the structure and assembly of thick filaments and their organization into the regular arrays of the A-band has recently been enhanced by the application of biochemical, genetic, and structural approaches. Detailed studies of the thick filament backbone have shown that the myosins are organized into a tubular structure. Additional protein machines and specific myosin rod sequences have been identified that play significant roles in thick filament structure, assembly, and organization. These include intrinsic filament components, cross-linking molecules of the M-band and constituents of the membrane-cytoskeleton system. Muscle organization is directed by the multistep actions of protein machines that take advantage of well-established self-assembly relationships. Copyright 1999 John Wiley & Sons, Inc.

NASA Discipline Musculoskeletal↗

Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading

The objective of this study was to determine whether altered intracellular Ca(2+) handling contributes to the specific force loss in the soleus muscle after unloading and/or subsequent reloading of mouse hindlimbs. Three groups of female ICR mice were studied: 1) unloaded mice (n = 11) that were hindlimb suspended for 14 days, 2) reloaded mice (n = 10) that were returned to their cages for 1 day after 14 days of hindlimb suspension, and 3) control mice (n = 10) that had normal cage activity. Maximum isometric tetanic force (P(o)) was determined in the soleus muscle from the left hindlimb, and resting free cytosolic Ca(2+) concentration ([Ca(2+)](i)), tetanic [Ca(2+)](i), and 4-chloro-m-cresol-induced [Ca(2+)](i) were measured in the contralateral soleus muscle by confocal laser scanning microscopy. Unloading and reloading increased resting [Ca(2+)](i) above control by 36% and 24%, respectively. Although unloading reduced P(o) and specific force by 58% and 24%, respectively, compared with control mice, there was no difference in tetanic [Ca(2+)](i). P(o), specific force, and tetanic [Ca(2+)](i) were reduced by 58%, 23%, and 23%, respectively, in the reloaded animals compared with control mice; however, tetanic [Ca(2+)](i) was not different between unloaded and reloaded mice. These data indicate that although hindlimb suspension results in disturbed intracellular Ca(2+) homeostasis, changes in tetanic [Ca(2+)](i) do not contribute to force deficits. Compared with unloading, 24 h of physiological reloading in the mouse do not result in further changes in maximal strength or tetanic [Ca(2+)](i).

NASA Program Biomedical Research and Countermeasur↗

Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution

Because resistance exercise (REx) and bed-rest unloading (BRU) are associated with opposing adaptations, our purpose was to test the efficacy of REx against the effects of 14 days of BRU on the knee-extensor muscle group. Sixteen healthy men were randomly assigned to no exercise (NoEx; n = 8) or REx (n = 8). REx performed five sets of leg press exercise with 80-85% of one repetition maximum (1 RM) every other day during BRU. Muscle samples were removed from the vastus lateralis muscle by percutaneous needle biopsy. Myofiber distribution was determined immunohistochemically with three monoclonal antibodies against myosin heavy chain (MHC) isoforms (I, IIa, IIx). MHC distribution was further assessed by quantitative gel electrophoresis. Dynamic 1-RM leg press and unilateral maximum voluntary isometric contraction (MVC) were determined. Maximal neural activation (root mean squared electromyogram) and rate of torque development (RTD) were measured during MVC. Reductions (P < 0.05) in type I (15%) and type II (17%) myofiber cross-sectional areas were found in NoEx but not in REx. Electrophoresis revealed no changes in MHC isoform distribution. The percentage of type IIx myofibers decreased (P < 0.05) in REx from 9 to 2% and did not change in NoEx. 1 RM was reduced (P < 0.05) by 9% in NoEx but was unchanged in REx. MVC fell by 15 and 13% in NoEx and REx, respectively. The agonist-to-antagonist root mean squared electromyogram ratio decreased (P < 0.05) 19% in REx. RTD slowed (P < 0.05) by 54% in NoEx only. Results indicate that REx prevented BRU-induced myofiber atrophy and also maintained training-specific strength. Unlike spaceflight, BRU did not induce shifts in myosin phenotype. The reported benefits of REx may prove useful in prescribing exercise for astronauts in microgravity.

NASA Discipline Musculoskeletal↗

Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms

This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

Non-NASA Center↗

Buckling Pneumatic Linear Actuators Inspired by Muscle

To being, the mechanical features of biological muscles are difficult to reproduce completely in synthetic systems. A new class of soft pneumatic structures (vacuum-actuated muscle-inspired pneumatic structures) is described that combines actuation by negative pressure (vacuum), with cooperative buckling of beams fabricated in a slab of elastomer, to achieve motion and demonstrate many features that are similar to that of mammalian muscle.

36 MATERIALS SCIENCE↗

Quantification of fat and skeletal muscle tissue at abdominal computed tomography: associations between single-slice measurements and total compartment volumes

Purpose: Body composition is of great prognostic value in several severe diseases, including different types of cancer as well as cardiometabolic disorders. We aimed to investigate the correlations of skeletal muscle mass and abdominal adipose tissue compartments between volumetric and single-slice measurements to study the usefulness of several anatomical landmarks for estimation of total compartment volumes using abdominal CT-scans. Methods: In this retrospective study volumetric quantifications of paraspinal skeletal muscles (SM) and adipose tissue compartments (visceral adipose tissue, VAT; subcutaneous adipose tissue, SAT) were performed in 50 consecutive patients (26 male; mean age, 63 ± 15 years) who underwent abdominal multislice-CT for diagnostic purposes using an in-house software. Associations between total volumes of SM, VAT, and SAT with single-slice measurements at eight predefined anatomical landmarks (median intervertebral disk spaces T12/L1 to L5/S1; level of the umbilicus (U); level of the radix of the superior mesenteric artery (SMA)) were studied using correlation coefficients. Results: Statistical analysis revealed a strong association between single-slice measurements of adipose tissue compartments with total VAT and SAT volume (VAT: all r > 0.89, P < 0.001; SAT: all r > 0.95, P < 0.001). The strongest associations with total SM volume were found for single-slice measurements obtained at L3/4 (r = 0.94, P < 0.001) and were further improved by normalization to height (r = 0.98, P < 0.001). Conclusions: Single-slice measurements of SM, VAT, and SAT at several anatomical landmarks are strongly associated with total compartment volumes and therefore allow for easy and simultaneous assessment of skeletal muscle mass and adipose tissue compartment volumes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A new anti-tumor strategy based on in vivo tumstatin overexpression after plasmid electrotransfer in muscle

Highlights: ► A new therapeutic strategy based on tumstatin in vivo overexpression is proposed. ► pVAX1©–tumstatin electrotransfer in muscle mediates protein expression in muscle. ► A substantial expression of tumstatin is detected in the serum of electrotransfected mice. ► Tumstatin overexpression decreases tumor growth and increases mouse survival. -- Abstract: The NC1 domains from the different α(IV) collagen chains were found to exert anti-tumorigenic and/or anti-angiogenic activities. A limitation to the therapeutic use of these matrikines is the large amount of purified recombinant proteins, in the milligram range in mice that should be administered daily throughout the experimental procedures. In the current study, we developed a new therapeutic approach based on tumstatin (NC1α3(IV)) overexpression in vivo in a mouse melanoma model. Gene electrotransfer of naked plasmid DNA (pDNA) is particularly attractive because of its simplicity, its lack of immune responsiveness and its safety. The pDNA electrotransfer in muscle mediates a substantial gene expression that lasts several months. A pVAX1© vector containing the tumstatin cDNA was injected into the legs of C57BL/6 mice and submitted to electrotranfer. Sera were collected at different times and tumstatin was quantified by ELISA. Tumstatin secretion reached a plateau at day 21 with an expression level of 12 μg/mL. For testing the effects of tumstatin expression on tumor growth in vivo, B16F1 melanoma cells were subcutaneously injected in mice 7 days after empty pVAX1© (Mock) or pVAX1©–tumstatin electrotransfer. Tumstatin expression triggered a large decrease in tumor growth and an increase in mouse survival. This new therapeutic approach seems promising to inhibit tumor progression in vivo.

60 APPLIED LIFE SCIENCES↗

Key role of microRNA-15a in the KLF4 suppressions of proliferation and angiogenesis in endothelial and vascular smooth muscle cells

Highlights: •This is the first demonstration that miR-15a is a novel target gene of KLF4. •A novel finding that KLF4 increases the expression of miR-15a in ECs and VSMCs. •The novel mechanism is that KLF4 inhibits the proliferation of ECs via miR-15a. •The novel mechanism is that KLF4 inhibits the proliferation of VSMCs via miR-15. •miR-15a mediates the anti-angiogenic activity of KLF4. -- Abstract: While recent insights indicate that the transcription factor Krüppel-like factor 4 (KLF4) is indispensable for vascular homeostasis, its exact role in proliferation and angiogenesis and how it functions remain unresolved. Thus, the aim of the present study was to evaluate the role of KLF4 in the proliferations of endothelial and vascular smooth muscle cells, as well as the angiogenesis. The overexpression of KLF4 in endothelial cells significantly impaired tube formation. KLF4 inhibited the formation of a vascular network in implanted Matrigel plugs in nude mice. Importantly, we found that KLF4 significantly upregulated the miR-15a expression in endothelial cells and vascular smooth muscle cells, and conversely, KLF4 depletion reduced the amount of miR-15a. Furthermore, KLF4 blocked cell cycle progression and decreased cyclin D1 expression in endothelial cells and vascular smooth muscle cells through the induction of miR-15a. Intriguingly, the delivery of a miR-15a antagomir to nude mice resulted in marked attenuation of the anti-angiogenic effect of KLF4. Collectively, our present study provide the first evidence that miR-15a as a direct transcriptional target of KLF4 that mediates the anti-proliferative and anti-angiogenic actions of KLF4, which indicates that KLF4 upregulation of miR-15a may represent a therapeutic option to suppress proliferative vascular disorders.

60 APPLIED LIFE SCIENCES↗

Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe{sup −/−} mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe{sup −/−} mice. In conclusion, statins mediate anti-atherogenic effects through PPARγ activation in SMCs. These effects of statins on SMCs may be beneficial for the prevention of atherosclerosis.

60 APPLIED LIFE SCIENCES↗