Lineage Analysis in Pulmonary Arterial Hypertension
Lineage Analysis in Pulmonary Arterial Hypertension
Peter Kao, M.D., Ph.D., Stanford University. Dr. Kao is a CDMRP-funded investigator supported by the DoD Peer Reviewed Medical Research Program (PRMRP).
Content
8.85 -> the title the DoD grant was lineage
11.71 -> analysis in pulmonary hypertension in
14.59 -> contrast to systemic hypertension
17.55 -> pulmonary hypertension is characterized
22.15 -> by a cellular overgrowth in the center
25.329 -> of the vessels the most important
28.3 -> question to some and the basis of the
31.329 -> grant is what is the nature and origin
34.21 -> of the pathologic cell that's
36.67 -> proliferating in the center of the blood
38.98 -> vessels and obstructing the lumen of the
40.69 -> blood vessels so we start with mice that
45.13 -> carry fluorescent reporters and so these
48.67 -> mice have been engineered so initially
50.59 -> every cell expresses a red fluorescent
53.83 -> protein tomato and only those cells that
58.87 -> are differentiated endothelial cells
60.67 -> they've switched the tomato red color to
63.28 -> a green fluorescent color what we're
66.009 -> seeing here is the inside of the
70.57 -> capillaries in an alveolus of the mouse
73.749 -> lung outlined here is a small pulmonary
77.679 -> artery the blue stain is a daffy nuclear
81.909 -> stain and we also have a teal color and
84.609 -> the teal is an immuno stain that detects
89.139 -> smooth muscle actin what these panels
91.99 -> are showing is that the green
93.999 -> endothelial cells a subset of them
95.859 -> around small pulmonary arteries actually
98.049 -> express smooth muscle actin so this is a
100.539 -> new discovery a subset of green
103.539 -> endothelial cells around pulmonary
105.159 -> arteries are expressing the teal smooth
106.719 -> muscle actin
108.479 -> during the injury process subsequent to
111.34 -> the development of experimental
112.689 -> pulmonary potential mouse gets a
114.67 -> pneumonectomy subsequently gets injected
117.34 -> with monochrome and parole six to ten
120.009 -> weeks later develops moderate pulmonary
122.049 -> hypertension when we look at the
123.61 -> pathology of that Mouse we see that
126.1 -> vessels are cross-sectionally filled in
129.91 -> with green cells representing
134.35 -> endothelial genetic lineage and when we
136.75 -> stained with the antibodies smooth
138.37 -> muscle actin we see that those luminal
140.95 -> obliterating the pathologic cells in
142.989 -> this disease are also expressing smooth
145.269 -> muscle actin this is the power of the
148.09 -> confocal microscopy we can go through a
152.61 -> physical section and take the time to
156.76 -> determine the co-localization of the
159.85 -> teal color the smooth muscle actin on
162.069 -> top of the GFP color the genetic lineage
164.68 -> marking in the endothelial cells and you
166.93 -> can see that the injured vessel really
169.87 -> has some luminol narrow in it's it's
172.09 -> it's crawling in and compare that to the
174.1 -> normal capillaries in the alveoli out
175.93 -> here and I would hope to extend our
180.489 -> studies from the animal model and scream
183.34 -> for therapies and drugs that would
185.89 -> attenuate the inappropriate smooth
188.56 -> muscle gene expression in the
190.45 -> endothelial cells so it's not quite anti
193.03 -> proliferation and it's not quite
195.37 -> vasodilation but it's more of a
197.29 -> redirection back towards an endothelial
200.23 -> phenotype
205.47 -> you
Source: https://www.youtube.com/watch?v=eOEQvYtfcKU