cellular senescence blog: smooth muscle

The following is a list of papers demonstrating cellular senescence in cell types other than fibroblasts. It will gradually be up-dated.

Endothelial cells

Vascular endothelial senescence: from mechanisms to pathophysiology. Erusalimsky JD. J Appl Physiol. 2009 Jan;106(1):326-32. Epub 2008 Nov 26.

Telomere attrition and accumulation of senescent cells in cultured human endothelial cells. Hastings R, Qureshi M, Verma R, Lacy PS, Williams B. Cell Prolif. 2004 Aug;37(4):317-24

Endothelial Cell Senescence in Human Atherosclerosis. Minamino et al. Circulation. 2002;105:1541.)

A cell kinetic analysis of human umbilical vein endothelial cells. Kalashnik et al. Mech Ageing Dev. 2000 Dec 1;120(1-3):23-32.

Vascular smooth muscle cells

Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Matthews et al, Circ Res. 2006 Jul 21;99(2):156-64. Epub 2006 Jun 22

Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification. Burton et al (2009) Experimental gerontology 2009 Oct;44(10):659-65 PubMed ID:(19631729)

Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transition. Nakano-Kurimoto et al, Am J Physiol Heart Circ Physiol. 2009 Sep 11. [Epub ahead of print]

Epithelial cells

Beta-galactosidase histochemistry and telomere loss in senescent retinal pigment epithelial cells. Matsunaga et al, Invest Ophthalmol Vis Sci. 1999 Jan;40(1):197-202

T-cells

T cell replicative senescence: pleiotropic effects on human aging. Effros RB, Ann N Y Acad Sci. 2004 Jun;1019:123-6

The role of CD8+ T-cell replicative senescence in human aging. Effros RB, Dagarag M, Spaulding C, Man J. Immunol Rev. 2005 Jun;205:147-57

Microglia

Microglial senescence: does the brain's immune system have an expiration date? Streit WJ Trends Neurosci. 2006 Sep;29(9):506-10. Epub 2006 Jul 20

The role of microglial cellular senescence in the aging and Alzheimer diseased brain. Flanary B, Rejuvenation Res. 2005 Summer;8(2):82-5

Astrocytes

Astrocytes aged in vitro show a decreased neuroprotective capacity. Pertusa et al, J Neurochem. 2007 May;101(3):794-805. Epub 2007 Jan 23

Osteoblasts

Demonstration of cellular aging and senescence in serially passaged long-term cultures of human trabecular osteoblasts. Kassem et al. Osteoporos Int. 1997;7(6):514-24.

Relationship between periarticular osteoporosis and osteoblast senescence in patients with rheumatoid arthritis. Yudoh K, Matsuno H, Kimura T., Clin Calcium. 2001 May;11(5):612-8

Chondrocytes

Aging, articular cartilage chondrocyte senescence and osteoarthritis. Martin and Buckwalter, Biogerontology. 2002;3(5):257-64

Pancreatic Beta cells

Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Sone H, Kagawa Y., Diabetologia. 2005 Jan;48(1):58-67. Epub 2004 Dec 29

Hepatocytes

Role of replicative senescence in the progression of fibrosis in hepatitis C virus (HCV) recurrence after liver transplantation. Trak-Smayra et al, Transplantation. 2004 Jun 15;77(11):1755-60

Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. Wiemann et al, FASEB J. 2002 Jul;16(9):935-42

Renal cells

Increased expression of senescence-associated cell cycle inhibitor p16INK4a in deteriorating renal transplants and diseased native kidney. Melk et al, Am J Transplant. 2005 Jun;5(6):1375-82

Stem/Progenitor cells

Replicative senescence of mesenchymal stem cells: a continuous and organized process. Wagner et al, PLoS ONE. 2008 May 21;3(5):e2213

Premature senescence of highly proliferative endothelial progenitor cells is induced by tumor necrosis factor-alpha via the p38 mitogen-activated protein kinase pathway. Zhang et al, FASEB J. 2009 May;23(5):1358-65. Epub 2009 Jan 5

Overview of atherosclerosis

Cardiovascular disease accounts for approximately 56% of the total mortality in the over 65 age group and represents the single largest age-related cause of death (Brock et al, 1990, Mills et al). Atherosclerosis constitutes the single most important contributor to this increasing problem of cardiovascular disease. Atherogenesis is a complicated process which includes endothelial cell (EC) dysfunction, smooth muscle cell (SMC) proliferation and migration, recruitment of inflammatory cells, lipid and matrix accumulation and thrombus formation (Tuomisto et al 2005).

To better understand the pathological processes that occur with atherosclerosis, an understanding of the structure of arteries is required. Human arteries are composed of three layers, the intima, the media and the adventitia. The intima is the innermost layer of the artery, composed of EC’s, SMC’s, macrophages and extracellular matrix (ECM) components. An internal elastic lamina separates the intima from the media, which is made up mainly of SMC. The adventitia is separated from the media by external elastic lamina and is mainly composed of fibroblasts and connective tissue.

The initiation and progression of atherosclerotic plaques generally takes place over many years during which the affected individual remains symptom free. Therefore, when a patient becomes symptomatic, the disease is already well established. These plaques occur at specific sites within arteries and these sites are dictated by fluid shear stress, the frictional force generated by blood flow over the vascular endothelium (Hwang et al, 2003). Regions of branched and curved arteries experience the greatest disturbed blood flow and it is at these sites that high incidences of plaque formation is found (VanderLaan et al, 2004). Relatively straight arteries however, experience the least shear stress and are usually protected from plaque development. Explanations for why high fluid stress sites are more “lesion-prone” is currently speculative.

The initial factors which result in the initiation of plaque formation are currently unknown. A common hypothesis is that plaque formation occurs as a result of EC damage leading to cellular dysfunction (Shimokawa, 1999, Davignon and Ganz, 2004). The source of the initial damage to EC’s is also currently unknown, but hypertension, viruses, toxins, smoking have all been suggested. Cellular dysfunction results in subsequent recruitment and accumulation of leukocytes and monocytes which would otherwise have resisted any adhesive interactions (Bobryshev et al, 2005). These adhered monocytes then differentiate into macrophages, engulf lipids, become foam cells and form fatty streaks. As the progression of the plaque continues, SMC’s migrate from the intima and synthesis extracellular matrix proteins in the intima (Boyle et al, 1997). Progressive macrophage accumulation, SMC migration and proliferation and extracellular matrix protein synthesis result in the formation of an advanced lesion.