1. Aging and Survival of Cutaneous Microvasculature
Edwin Chang, Jiwei Yang, Usha Nagavarapu, G. Scott Herron 
Journal of Investigative Dermatology 
Volume 118, Issue 5, Pages (May 2002)
DOI: /j x
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

2. Figure 1
Cellular proliferation, quiescence, apoptosis, and senescence are the four principal cytologic states that set the cutaneous microvascular in a dynamic balance between maintenance and remodeling. Actively growing and quiescent cells are the two reversible processes that would maintain a homeostasis between maintenance and vascular proliferation. Depending on the environmental conditions, EC in either quiescence or proliferation can move irreversibly into apoptosis (thus promoting remodeling) or into senescence. Cellular processes controlling EC survival are in a dynamic balance during remodeling and maintenance states of the microvasculature. Molecular mechanisms modulating EC proliferation and senescence must be balanced against competing processes of apoptosis and quiescence to maintain homeostasis and correct function during states of tissue stress (e.g., inflammation, wound repair, tumor growth, and environmental insults). According to theoretical notions on the contribution of cellular senescence to diseased states, EC that become senescent are regarded as having exited this homeostatic milieu and to have initiated a pathologic condition for the endothelium.
Journal of Investigative Dermatology  , DOI: ( /j x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

3. Figure 2
Manifold EC surface-associated signaling events converge on a common survival kinase cascade system involving PI3-K and Akt. Activation via phosphorylation of Akt by PI3-K, in turn, differentially affects multiple other signaling pathways with downstream targets known to affect EC survival (e.g., endothelial NO synthetase, Raf, p65PAK1·, and hTERT). Indirect blockade of apoptosis occurs via Akt-mediated phosphorylation of Bad, which does not bind bcl-2, allowing it to interact with bax and block caspase activation. p65PAK1· activation by other mechanisms directly affects phosphorylation of Bad, leading to the same result. A potential feedback loop(s) is apparent as telomerase-activation in EC leads to maintenance of activated Akt during induction of apoptosis (GSH, unpublished).
Journal of Investigative Dermatology  , DOI: ( /j x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

4. Figure 3
Telomeres cap the ends of chromosomes and represent specialized protein-nucleic acid structures with a unique DNA repeat sequence, TTAGGG. Mammalian DNA polymerase is unable to replicate near the ends of chromosomes and thus each round of cell division is associated with telomeric DNA shortening. The rate of shortening is unique in different tissues and cell types. Uncharacterized molecular sensing systems appear to monitor DNA damage at chromosomal ends such that at a critical length a gene expression program is activated, termed “cellular senescence”, in which cells become unresponsive to growth signals and express the senescence phenotype.
Journal of Investigative Dermatology  , DOI: ( /j x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

5. Figure 4
Visualization of human microvasculature created by xenografting telomerized HDMEC in SCID mice. Primary HDMEC were transduced with both eGFP and hTERT, FAC-sorted to purify fluorescent cells, and then subcutaneously implanted in SCID mice. After 2 wk, grafts were harvested and analyzed by IF microscopy. Fluorescent vascular structures prove the human origin of the microvessels and allow visualization of vessel morphology. Such a system represents an in vivo human cutaneous microvascular remodeling platform for analysis of EC survival mechanisms, wound repair, and vascular cell gene delivery.
Journal of Investigative Dermatology  , DOI: ( /j x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions