The Science behind Our Technology
The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway integrates signals from multiple receptor kinases to regulate cellular growth and metabolism. Regulation of the pathway is complex with internal feedback loops and horizontal cross-talks with parallel signal transduction pathways. Mechanisms for pathway activation include loss of tumor suppressor PTEN function, amplification or mutation of PI3K, amplification or mutation of Akt, activation of growth factor receptors, and exposure to carcinogens. The PI3K/Akt/mTOR pathway is attractive as a therapeutic target as kinases in the pathway are found to be activated with increased cellular functions, including cell-cycle progression, protein translation and transcription in a variety of diseases. Activation of the PI3K/Akt/mTOR pathway results in the stimulation of angiogenesis in diseases such as cancer, ophthalmic diseases (macular degeneration, diabetic retinopathy, proliferative vitreoretinopathy), skin diseases (atopic dermatitis, psoriasis, rosacea, photo-aging-wrinkling). Viruses use the pathway for replication. Central nervous system disorders include epilepsy (via signalling through tuberous sclerosis complex, TSC, of the pathway) and neurodegenerative disease (Parkinson's, Huntington's, Amyotrophic lateral sclerosis) through aberrant protein accumulation (autophagy, process of removal of such proteins may be dysregulated with pathway activation) and schizophrenia (through activation of GSK3b within the pathway).
Blood vessels that make up the cardiovascular system may be broadly divided into arteries, veins and capillaries. Arteries carry blood away from the heart at relatively high pressure; veins carry blood back to the heart at low pressure, while capillaries provide the link between the arterial and venous blood supply. During embryonic development, vessels are first formed through vasculogenesis, utilizing pluripotent endothelial cell precursors. Later, through arteriogenesis, larger blood vessels are formed possessing a more complex structure of endothelial cells, smooth muscle cells and pericytes (tunica media). Although arteriogenesis is not considered to occur in the adult, blood vessels may be formed in the adult through angiogenesis. Under normal conditions, angiogenic neovascularization occurs during such conditions as wound repair, ischemic restoration (ischemia is a restriction in blood supply generally due to factors in the blood vessels with resultant damage or dysfunction of tissue) after myocardial infarction and the female reproductive cycle (generating endometrium forming the corpus luteum and during pregnancy to create the placental). The capillaries, relatively simple vessels formed by angiogenesis, lack a developed tunica, as they are predominantly composed of endothelial cells, perivascular cells and basement membrane. If formed aberrantly, they may induce or promote a variety of pathological conditions, as described above.