Research Areas

The P. K. Shah Laboratory has identified a number of novel genes such as tenascin C, pleotrophin (PTN), GATA3 and KLF14 that have potential implications for inflammation, atherosclerosis and obesity-metabolic syndrome. We are currently evaluating their role in murine models of atherosclerosis, myocardial infarction, left ventricular remodeling and obesity.

Deletion of TNC gene in apo E−/− mice promotes adventitial accumulation of mast cells. The two mouse genotypes were fed an atherogenic diet for 24–28 weeks (10 mice genotype). The aorta including the periadventitia tissue around the aorta was used for paraffin embedding. Two staining methods were used to stain mast cells in the paraffin-embedded sections of the double KO mice: toluidine blue (panel A at 10× magnification and panel B at 40× magnification) and chloroacetate esterase (Panels C at 10× magnification and D at 40× magnification). Panels E and F show an aortic section from the control apo E−/− mice on high fat diet for 24–28 weeks that is stained with toluidine blue at 10× and 40 × magnifications, respectively. The 40× shows magnification of base of the plaque.
© 2015 Elsevier Inc.

Atherosclerosis is the leading cause of cardiovascular disease and death in men and women. The ultimate goal of our experimental studies is to develop novel therapies for this highly prevalent disease, which can then be tested in clinical trials. In that regard, the P. K. Shah Lab has developed two novel biologic therapies with the potential for revolutionizing the management of cardiovascular disease. The first involved the development of ApoA-1 Milano, a naturally occurring mutant of apolipoprotein A-1, with gain-of-function properties as a therapy to stabilize and reverse atherosclerosis using either infusion therapy or gene transfer. The infusion of ApoA-1 Milano is undergoing clinical testing at the present time.

Effects of p210 vaccine on IL-6, MCP-1 and CCR2 expression and macrophage infiltration in aorta. The messenger ribonucleic acid (mRNA) expression of (A) IL-6, (B) MCP-1, and (C) CCR2 in aortas as analyzed by quantitative real-time reverse transcription polymerase chain reaction. Number of mice: (A) PBS = 11, cBSA = 14, p210 = 10; (B) PBS = 7, cBSA = 10, p210 = 8; and (C)PBS = 12, cBSA = 13, p210 = 10. (D to F) Representative pictures of infiltration of macrophage in aneurysmal aortic wall assessed by monocyte/macrophage (MOMA)-2 immunohistochemical staining (reddish-brown stain) for mice in the (D) PBS, (E) cBSA, and (F) p210 groups. 10 × magnification; bar = 0.01 mm; the box highlights the area magnified at 20 × (inset in each photo). (G) Quantitative analysis of MOMA-2 staining in adventitia of aorta. All of the analyzed sections were from suprarenal aorta. Number of mice: PBS = 7, cBSA = 9, p210 = 8. *p < 0.05 versus p210; †p < 0.01 versus p210. AU = arbitrary units; CCR2 = chemokine receptor 2; MCP = monocyte chemotactic protein.
© 2015 Elsevier Inc.


The second major development involves the use of human ApoB-100-related antigens as vaccines to reduce atherosclerosis and vascular inflammation, aortic aneurysm rupture and hypertension. This approach is at a preclinical stage with the hope of moving into clinical testing in the near future.

Representative macrophage immunoreactivity in the innominate artery lesions of mice are shown (A to C) and are presented as quantitative data (D). The macrophage immunireactive area was significantly lower in recipients of apolipoprotein A-I Milano (A-IM) compared with vector controls (VC) or recipients of wild-type apolipoprotein A-I (A-I).
© 2015 Elsevier Inc.

The P. K. Shah Laboratory is also conducting clinical trials involving experimental non-statin cholesterol-lowering agents called PCSK9 inhibitors in patients with high cholesterol levels and statin intolerance.