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Identification of hemostatic genes expressed in human and rat leg muscles and a novel gene (LPP1/PAP2A) suppressed during prolonged physical inactivity (sitting).

Zderic TW, Hamilton MT - Lipids Health Dis (2012)

Bottom Line: The effects of inactivity during sitting are most alarming when a person develops the enigmatic condition in the legs called deep venous thrombosis (DVT) or "coach syndrome," caused in part by muscular inactivity.These include the fibrinolytic factors tetranectin, annexin A2, and tPA; the anti-coagulant factors TFPI, protein C receptor, PAF acetylhydrolase; coagulation factors, and genes necessary for the posttranslational modification of these coagulation factors such as vitamin K epoxide reductase.Of special interest, lipid phosphate phosphatase-1 (LPP1/PAP2A), a key gene for degrading prothrombotic and proinflammatory lysophospholipids, was suppressed locally in muscle tissue within hours after sitting in humans; this was also observed after acute and chronic physical inactivity conditions in rats, and exercise was relatively ineffective at counteracting this effect in both species.

View Article: PubMed Central - HTML - PubMed

Affiliation: Inactivity Physiology Department, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. theodore.zderic@pbrc.edu

ABSTRACT

Background: Partly because of functional genomics, there has been a major paradigm shift from solely thinking of skeletal muscle as contractile machinery to an understanding that it can have roles in paracrine and endocrine functions. Physical inactivity is an established risk factor for some blood clotting disorders. The effects of inactivity during sitting are most alarming when a person develops the enigmatic condition in the legs called deep venous thrombosis (DVT) or "coach syndrome," caused in part by muscular inactivity. The goal of this study was to determine if skeletal muscle expresses genes with roles in hemostasis and if their expression level was responsive to muscular inactivity such as occurs in prolonged sitting.

Methods: Microarray analyses were performed on skeletal muscle samples from rats and humans to identify genes associated with hemostatic function that were significantly expressed above background based on multiple probe sets with perfect and mismatch sequences. Furthermore, we determined if any of these genes were responsive to models of physical inactivity. Multiple criteria were used to determine differential expression including significant expression above background, fold change, and non-parametric statistical tests.

Results: These studies demonstrate skeletal muscle tissue expresses at least 17 genes involved in hemostasis. These include the fibrinolytic factors tetranectin, annexin A2, and tPA; the anti-coagulant factors TFPI, protein C receptor, PAF acetylhydrolase; coagulation factors, and genes necessary for the posttranslational modification of these coagulation factors such as vitamin K epoxide reductase. Of special interest, lipid phosphate phosphatase-1 (LPP1/PAP2A), a key gene for degrading prothrombotic and proinflammatory lysophospholipids, was suppressed locally in muscle tissue within hours after sitting in humans; this was also observed after acute and chronic physical inactivity conditions in rats, and exercise was relatively ineffective at counteracting this effect in both species.

Conclusions: These findings suggest that skeletal muscle may play an important role in hemostasis and that muscular inactivity may contribute to hemostatic disorders not only because of the slowing of blood flow per se, but also potentially because of the contribution from genes expressed locally in muscles, such as LPP1.

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Suppression of LPP1 gene expression in rat soleus caused by chronic physical inactivity. Rats were prevented from standing for 10 hrs/d for 11 consecutive days. Results for two independent sets of probes for LPP1 on the rat U34A microarray are presented. Probe set nomenclature is from Affymetrix.com. Results are expressed as mean ± SE. † Inactivity vs. Ambulatory Control, p < 0.05.
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Figure 1: Suppression of LPP1 gene expression in rat soleus caused by chronic physical inactivity. Rats were prevented from standing for 10 hrs/d for 11 consecutive days. Results for two independent sets of probes for LPP1 on the rat U34A microarray are presented. Probe set nomenclature is from Affymetrix.com. Results are expressed as mean ± SE. † Inactivity vs. Ambulatory Control, p < 0.05.

Mentions: In order to identify genes potentially governing hemostasis that are most robustly affected by physical inactivity (not standing/ambulating) and non-exercise physical activity, we performed a microarray analysis where we looked for genes with hemostatic functions in rats. A single gene was differentially expressed in the acute study (LPP1) and, similarly, a gene was differentially expressed in a chronic study (Figure1) (also LPP1). Interestingly, even exercise on a treadmill (30 minutes per hour) for 4 hours immediately following inactivity was not sufficient to rapidly restore LPP1 gene expression (Figure2).


Identification of hemostatic genes expressed in human and rat leg muscles and a novel gene (LPP1/PAP2A) suppressed during prolonged physical inactivity (sitting).

Zderic TW, Hamilton MT - Lipids Health Dis (2012)

Suppression of LPP1 gene expression in rat soleus caused by chronic physical inactivity. Rats were prevented from standing for 10 hrs/d for 11 consecutive days. Results for two independent sets of probes for LPP1 on the rat U34A microarray are presented. Probe set nomenclature is from Affymetrix.com. Results are expressed as mean ± SE. † Inactivity vs. Ambulatory Control, p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539950&req=5

Figure 1: Suppression of LPP1 gene expression in rat soleus caused by chronic physical inactivity. Rats were prevented from standing for 10 hrs/d for 11 consecutive days. Results for two independent sets of probes for LPP1 on the rat U34A microarray are presented. Probe set nomenclature is from Affymetrix.com. Results are expressed as mean ± SE. † Inactivity vs. Ambulatory Control, p < 0.05.
Mentions: In order to identify genes potentially governing hemostasis that are most robustly affected by physical inactivity (not standing/ambulating) and non-exercise physical activity, we performed a microarray analysis where we looked for genes with hemostatic functions in rats. A single gene was differentially expressed in the acute study (LPP1) and, similarly, a gene was differentially expressed in a chronic study (Figure1) (also LPP1). Interestingly, even exercise on a treadmill (30 minutes per hour) for 4 hours immediately following inactivity was not sufficient to rapidly restore LPP1 gene expression (Figure2).

Bottom Line: The effects of inactivity during sitting are most alarming when a person develops the enigmatic condition in the legs called deep venous thrombosis (DVT) or "coach syndrome," caused in part by muscular inactivity.These include the fibrinolytic factors tetranectin, annexin A2, and tPA; the anti-coagulant factors TFPI, protein C receptor, PAF acetylhydrolase; coagulation factors, and genes necessary for the posttranslational modification of these coagulation factors such as vitamin K epoxide reductase.Of special interest, lipid phosphate phosphatase-1 (LPP1/PAP2A), a key gene for degrading prothrombotic and proinflammatory lysophospholipids, was suppressed locally in muscle tissue within hours after sitting in humans; this was also observed after acute and chronic physical inactivity conditions in rats, and exercise was relatively ineffective at counteracting this effect in both species.

View Article: PubMed Central - HTML - PubMed

Affiliation: Inactivity Physiology Department, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. theodore.zderic@pbrc.edu

ABSTRACT

Background: Partly because of functional genomics, there has been a major paradigm shift from solely thinking of skeletal muscle as contractile machinery to an understanding that it can have roles in paracrine and endocrine functions. Physical inactivity is an established risk factor for some blood clotting disorders. The effects of inactivity during sitting are most alarming when a person develops the enigmatic condition in the legs called deep venous thrombosis (DVT) or "coach syndrome," caused in part by muscular inactivity. The goal of this study was to determine if skeletal muscle expresses genes with roles in hemostasis and if their expression level was responsive to muscular inactivity such as occurs in prolonged sitting.

Methods: Microarray analyses were performed on skeletal muscle samples from rats and humans to identify genes associated with hemostatic function that were significantly expressed above background based on multiple probe sets with perfect and mismatch sequences. Furthermore, we determined if any of these genes were responsive to models of physical inactivity. Multiple criteria were used to determine differential expression including significant expression above background, fold change, and non-parametric statistical tests.

Results: These studies demonstrate skeletal muscle tissue expresses at least 17 genes involved in hemostasis. These include the fibrinolytic factors tetranectin, annexin A2, and tPA; the anti-coagulant factors TFPI, protein C receptor, PAF acetylhydrolase; coagulation factors, and genes necessary for the posttranslational modification of these coagulation factors such as vitamin K epoxide reductase. Of special interest, lipid phosphate phosphatase-1 (LPP1/PAP2A), a key gene for degrading prothrombotic and proinflammatory lysophospholipids, was suppressed locally in muscle tissue within hours after sitting in humans; this was also observed after acute and chronic physical inactivity conditions in rats, and exercise was relatively ineffective at counteracting this effect in both species.

Conclusions: These findings suggest that skeletal muscle may play an important role in hemostasis and that muscular inactivity may contribute to hemostatic disorders not only because of the slowing of blood flow per se, but also potentially because of the contribution from genes expressed locally in muscles, such as LPP1.

Show MeSH
Related in: MedlinePlus