AMP-activated protein kinase, stress responses and cardiovascular diseases

Wang, Shaobin; Song, Ping

doi:10.1042/cs20110625

Cited by 205 publications

(169 citation statements)

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“…It is also known as a stress sensor and can be activated by intracellular ROS under various conditions, including exposure to hypoxia (59). Generally, the activation of AMPK turns on catabolic pathways that generate ATP while inhibiting cell proliferation and biosynthetic processes that consume ATP (59). Activation of AMPK was found to contribute to elevated [Ca 21 ] i response to hypoxia through activation of store-operated calcium entry.…”

Section: Discussionmentioning

confidence: 99%

“…AMPK is well known as an energy sensor and can be activated by increased cellular AMP levels. It is also known as a stress sensor and can be activated by intracellular ROS under various conditions, including exposure to hypoxia (59). Generally, the activation of AMPK turns on catabolic pathways that generate ATP while inhibiting cell proliferation and biosynthetic processes that consume ATP (59).…”

Section: Discussionmentioning

confidence: 99%

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Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Wang

Qian

Wan

et al. 2013

Am J Respir Cell Mol Biol

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Danshen, the dried root of Salvia miltiorrhiza, is widely used in clinics in China for treating various diseases, including cardiovascular diseases. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca 21 concentration ([Ca 21 ] i ) and store-operated Ca 21 entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn 21 quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O 2 , 21 d) was increased by 59%, and basal [Ca 21 ] i was increased by 119%; this effect was inhibited by intraperitoneal injection of STS. These inhibitory effects of STS on hypoxic increases of SOCE and basal [Ca 21 ] i were associated with reduced expression of canonical transient receptor potential (TRPC)1 and TRPC6 in distal pulmonary arterial smooth muscle and decreases on right ventricular pressure, right ventricular hypertrophy, and peripheral pulmonary vessel thickening. In ex vivo cultured distal PASMCs from normoxic rats, STS (0-25 mM) dose-dependently inhibited hypoxiainduced cell proliferation and migration, paralleled with attenuation in increases of basal [Ca 21 ] i , SOCE, mRNA, and protein expression of TRPC1 and TRPC6. STS also relieved right ventricular systolic pressure, right ventricular hypertrophy, and TRPC1 and TRPC6 protein expression in distal pulmonary arteries in a monocrotaline-induced rat model of pulmonary arterial hypertension. These results indicate that STS prevents pulmonary arterial hypertension development likely by inhibiting TRPC1 and TRPC6 expression, resulting in normalized basal [Ca 21 ] i and attenuated proliferation and migration of PASMCs.Keywords: STS; TRPC; SOCE; pulmonary hypertension Pulmonary arterial hypertension (PAH) is a rare yet life-threatening disease that affects 15 per 1 million adults, according to the most recent estimation in 2008 (1). It is physiologically defined by mean pulmonary arterial pressure of 25 mm Hg or greater at rest and is pathologically characterized by pulmonary vascular remodeling, including smooth muscle hypertrophy and intima thickening. Although significant progress has been made in the past decades in our understanding of PAH and in disease management, the prognosis is still poor, with a 1-year survival rate of 91.0% (2) and 3-year survival rate of 77% or less according to recent investigations (3-5). The principal treatments for PAH rely on approaches targeting the prostacyclin, endothelin, or NO pathways (phosphodiesterase inhibition) or, increasingly, on a combination of them (6-11). Few patients show indication for treatment with calcium channel...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Wang

Qian

Wan

et al. 2013

Am J Respir Cell Mol Biol

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“…These potential direct actions of metformin on vascular tissues are thought to be mediated, at least in part, by activation of AMP-activated protein kinase (AMPK) [79,80]. AMPK mimics insulin's action in cardiovascular tissues by phosphorylation and activation of eNOS, stimulating NO synthesis in addition to NO-dependent and NO-independent suppression of endothelial pro-inflammatory signaling [81,82].…”

Section: Direct Vascular Actions Of Antidiabetic Pharmaceuticalsmentioning

confidence: 99%

Examining the Role of Insulin in the Regulation of Cardiovascular Health

Salt

2012

Future Cardiol.

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Examining the role of insulin in the regulation of cardiovascular health SUMMARYA substantial body of evidence has reported insulin has direct actions on the cardiovascular system independent of its systemic effects on plasma glucose or lipids. In particular, insulin regulates endothelial synthesis of the vasoactive mediators nitric oxide and endothelin-1, yet the importance of this in the maintenance of cardiovascular health remains poorly understood.Recent studies using animals with targeted downregulation of insulin signaling in vascular tissues are improving our understanding of the role of insulin in vascular health. This article focuses on the direct actions of insulin in cardiovascular tissues, with particular emphasis on the molecular mechanisms of insulin action on endothelial function. The potential contribution of impaired vascular insulin action to the cardiovascular complications of diabetes will also be discussed.

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“…Together, HIF‐1 and AMPK activation are believed to be important for cellular survival (Wang et al. 2012). Previously, we demonstrated that pharmacological activation of AMPK increases Cr transport capacity in cultured cardiomyocytes (Darrabie et al.…”

Section: Discussionmentioning

confidence: 99%

“…Together, the activation of AMPK and HIF‐1 signaling pathways are thought to constitute a functional axis critical for the survival of cell exposed to hypoxia (Wang et al. 2012). …”

Section: Introductionmentioning

confidence: 99%

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation

et al. 2017

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Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m. Pharmacological activation of AMP‐activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF‐1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF‐1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia.

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AMP-activated protein kinase, stress responses and cardiovascular diseases

Cited by 205 publications

References 233 publications

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Examining the Role of Insulin in the Regulation of Cardiovascular Health

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation

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