Telomere stabilization by metformin mitigates the progression of atherosclerosis via the AMPK-dependent p-PGC-1α pathway.

Telomere dysfunction is a well-known molecular trigger of senescence and has been associated with various age-related diseases, including atherosclerosis. However, the mechanisms involved have not yet been elucidated, and the extent to which telomeres contribute to atherosclerosis is unknown. Therefore, we investigated the mechanism of metformin-induced telomere stabilization and the ability of metformin to inhibit vascular smooth muscle cell (VSMC) senescence caused by advanced atherosclerosis.

SIRT1-dependent PGC-1α deacetylation by SRT1720 rescues progression of atherosclerosis by enhancing mitochondrial function.

Vascular smooth muscle cell (VSMC) senescence promotes atherosclerosis via lipid-mediated mitochondrial dysfunction and oxidative stress. However, the mechanisms of mitochondrial dysfunction and VSMC senescence in atherosclerosis have not been established. Here, we investigated the mechanisms whereby signaling pathways regulated by SRT1720 enhance or regulate mitochondrial functions in atherosclerotic VSMCs to suppress atherosclerosis.

PPARγ activation by fisetin mitigates vascular smooth muscle cell senescence via the mTORC2-FoxO3a-autophagy signaling pathway.

Cellular senescence is caused by diverse stimuli and contributes to cardiovascular diseases. Several studies have indicated that PPARγ acts as a key mediator of lipid metabolism and shown that it has a protective effect on vascular biology. Nevertheless, the mechanism responsible for the anti-aging effects of PPARγ has not been fully elucidated in vascular smooth muscle cell (VSMC).

Fisetin alleviates cellular senescence through PTEN mediated inhibition of PKCδ-NOX1 pathway in vascular smooth muscle cells.

Reactive oxygen species (ROS) are a key risk factor of cellular senescence and age-related diseases, and protein kinase C (PKC) has been shown to activate NADPH oxidases (NOXs), which generate ROS. Although PKC activation induces oxidative stress, leading to the cellular dysfunction in various cell types, the correlation between PKC and senescence has not been reported in vascular smooth muscle cell (VSMC). Several studies have indicated cellular senescence is accompanied by phosphatase and tensin homolog (PTEN) loss and that an interaction exists between PTEN and PKC.

Metformin mitigates stress-induced premature senescence by upregulating AMPKα at Ser485 phosphorylation induced SIRT3 expression and inactivating mitochondrial oxidants.

The senescence of vascular smooth muscle cells (VSMCs) is an important cause of cardiovascular disease such as atherosclerosis and hypertension. These senescence may be triggered by many factors, such as oxidative stress, inflammation, DNA damage, and senescence-associated secretory phenotypes (SASPs). Mitochondrial oxidative stress induces cellular senescence, but the mechanisms by which mitochondrial reactive oxygen species (mtROS) regulates cellular senescence are still largely unknown.

Fisetin-induced PTEN expression reverses cellular senescence by inhibiting the mTORC2-Akt Ser473 phosphorylation pathway in vascular smooth muscle cells.

Cellular senescence is caused by a wide range of intracellular and extracellular stimuli and influences physiological functions, leading to the progression of age-related diseases. Many studies have shown that cellular senescence is related to phosphatase and tension homolog deleted on chromosome ten (PTEN) loss and mammalian target of rapamycin (mTOR) activation. Although it has been reported that mTOR complex 1 (mTORC1) is major anti-aging target in several cell types, the functions and mechanisms of mTOR complex 2 (mTORC2) during aging have not been elucidated in vascular smooth muscle cells (VSMCs).

SIRT1 suppresses cellular senescence and inflammatory cytokine release in human dermal fibroblasts by promoting the deacetylation of NF-κB and activating autophagy.

Skin aging is a complex process and involves extrinsic and intrinsic processes with distinct characteristics. Understanding skin aging requires knowledge of the senescence of human dermal fibroblasts (HDFs) and the biological mechanisms involved in this process. However, the molecular mechanism responsible for the aging of HDFs is still not clear.

Prednisolone suppresses adriamycin-induced vascular smooth muscle cell senescence and inflammatory response via the SIRT1-AMPK signaling pathway.

Cellular senescence is associated with inflammation and the senescence-associated secretory phenotype (SASP) of secreted proteins. Vascular smooth muscle cell (VSMC) expressing the SASP contributes to chronic vascular inflammation, loss of vascular function, and the developments of age-related diseases. Although VSMC senescence is well recognized, the mechanism of VSMC senescence and inflammation has not been established.

Nifedipine-induced AMPK activation alleviates senescence by increasing autophagy and suppressing of Ca levels in vascular smooth muscle cells.

Calcium (Ca) homeostasis is disrupted during aging in several cell types and this disruption leads to autophagy impairment. The mechanisms regarding Ca, senescence, and autophagy need to be elucidated. Therefore, we hypothesized that cellular senescence can be improved by regulating Ca level and autophagy activity.

Apelin-13 Inhibits Methylglyoxal-Induced Unfolded Protein Responses and Endothelial Dysfunction via Regulating AMPK Pathway.

It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction than glucose itself. Recent reports showed that high glucose and MGO induced endoplasmic reticulum (ER) stress and myocyte apoptosis in ischemic heart disease was inhibited by apelin. The goal of the study is to investigate the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress in endothelial cells, and to examine whether apelin-13, a cytoprotective polypeptide ligand, protects MGO-induced aortic endothelial dysfunction.

SRT1720-induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA-dependent phosphorylation of AMPKα at Ser485.

Aging is a major risk factor for hypertension and atherosclerosis, and vascular smooth muscle cell (VSMC) senescence can promote aging-related vascular diseases. Sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) were previously reported to modulate vascular senescence; however, its effects have not been well characterized. To determine the nature of the interaction between SIRT1 and AMPK in VSMC senescence, we investigated the effects of SRT1720 on its downstream targets of SIRT1 and the phosphorylation of AMPKα at Ser485.

Quercetin-induced apoptosis ameliorates vascular smooth muscle cell senescence through AMP-activated protein kinase signaling pathway.

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells.

Gliclazide, a K channel blocker, inhibits vascular smooth muscle cell proliferation through the CaMKKβ-AMPK pathway.

Gliclazide, a sulfonylurea that is widely used to treat type II-diabetes, specifically blocks K channels and recombinant smooth muscle (SUR2B/Kir6.1) K channels with high potency. Furthermore, it exerts antioxidant properties and inhibits tumor cell proliferation.

Quercetin-Induced AMP-Activated Protein Kinase Activation Attenuates Vasoconstriction Through LKB1-AMPK Signaling Pathway.

The vascular tone plays an important role in blood pressure and flow. It is influenced by the contraction of vascular smooth muscle cells (VSMCs), which in turn is regulated by the balance between the myosin light chain kinase (MLCK) and the phosphorylated myosin light chain (p-MLC). Quercetin is a common flavonoid which is found in many fruits and red wine.

Interaction between mTOR pathway inhibition and autophagy induction attenuates adriamycin-induced vascular smooth muscle cell senescence through decreased expressions of p53/p21/p16.

Cellular senescence is related to aging and extremely stable proliferative arrest with active metabolism. Senescent cells can activate mammalian target of rapamycin (mTOR) pathway, which plays a crucial role in the regulation of cell metabolism, cellular growth, and autophagy in senescence-associated cardiovascular diseases. Therefore, we examined whether mTOR pathway could induce cellular senescence by inhibition of autophagy in vascular smooth muscle cells (VSMCs).

Preparation and in vivo evaluation of lecithin-based microparticles for topical delivery of minoxidil.

Minoxidil is widely used for treatment of androgenic alopecia. Commercial products containing minoxidil are usually in solution form. Repeated applications of minoxidil solution can lead to adverse effects such as skin irritation and horniness.

Laminar shear stress suppresses vascular smooth muscle cell proliferation through nitric oxide-AMPK pathway.

In healthy condition, vascular smooth muscle cells (VSMCs) are not directly exposed to shear stresses, because they are shielded by endothelial cell (EC) layer that lines blood vessels. After injury to EC layer caused by rupture of atherosclerotic lesions or invasive techniques such as angioplasty, VSMCs are directly exposed to blood flow which modulate molecular signaling and function. In endothelium, exposure to fluid shear stress has been reported to induce AMP-activated protein kinase (AMPK) phosphorylation and nitric oxide (NO) production.

Activated protein C prevents methylglyoxal-induced endoplasmic reticulum stress and cardiomyocyte apoptosis via regulation of the AMP-activated protein kinase signaling pathway.

Previous epidemiological studies have shown that methylglyoxal (MGO) levels are highly regulated in diabetic cardiovascular diseases. We have also previously reported that MGO mediates ER stress and apoptosis in cardiomyocytes. Furthermore, activated protein C (APC) has recently been shown to play a protective role against ER stress, as well as a cardioprotective role against ischemia and reperfusion injury by augmenting the AMP-activated protein kinase (AMPK) signaling pathway.

Estrogenic compound attenuates angiotensin II-induced vascular smooth muscle cell proliferation through interaction between LKB1 and estrogen receptor α.

The prevalence rate of cardiovascular disease is higher for males than females, and estradiol (E2) induces AMP-activated protein kinase (AMPK) activation, which is known to regulate proliferation of VSMC. We identified the estrogenic properties of nordihydroguaiaretic acid (NDGA, a lignan phytoestrogen) that inhibit VSMC proliferation and explored the underlying mechanisms. Both the phosphorylation and expression of LKB1 were increased by NDGA.

Genistein-induced LKB1-AMPK activation inhibits senescence of VSMC through autophagy induction.

Genistein, the primary isoflavone from soy products, enhances antioxidant enzyme activities and inhibits tyrosine kinase. However, the mechanisms underlying genistein-induced autophagy are not yet completely understood. Autophagy refers to a regulated cellular process for the lysosomal-dependent turnover of organelles and proteins.

Mesoglycan attenuates VSMC proliferation through activation of AMP-activated protein kinase and mTOR.

Background: Vascular smooth muscle cells (VSMC) proliferation contributes significantly to intimal thickening in atherosclerosis and restenosis diseases. Platelet derived growth factor (PDGF) has been implicated in VSMC proliferation though the activation of multiple growth-promoting signals. Mesoglycan, a natural glycosaminoglycans preparation, is reported to show vascular protective effect.

ERK5 regulates basic fibroblast growth factor-induced type 1 plasminogen activator inhibitor expression and cell proliferation in lung fibroblasts.

Aims: bFGF is a potent mitogen of cells associated with fibrosis. Although ERK5 has been reported to play roles in the development of fibrosis, its roles in regulating bFGF-induced fibrotic responses are not understood, especially in lung fibroblasts. The authors investigated the role of ERK5 in bFGF induction of cell proliferation and in induction of PAI-1, a critical regulator of the pathological features of fibrosis, in lung fibroblasts.