Mobilization of EPCs after myocardial infarction. Shintani

1
Endothelial Progenitor Cells (EPCs)
2
EPCs in CV diseases
EPCs
Therapeutics
Pathophysiology
Atherosclerosis Heart disease Peripheral vascular
disease
Courtesy of Arshed A. Quyyumi, MD.
3
Circulating EPCs aid in cardiac repair

• CD34, CD133, and VEGF2R
• Circulate in blood stream
• Contribute to repair of vascular or myocardial
  injury and collateral formation

Asahara T et al. Science. 1997275964-7. Takahash
i T et al. Nature Med. 19995434-8.
4
EPC physiology

• Originate in bone marrow
• Circulate in blood stream
• Number and function (proliferation, migration,
  homing) modulated by age, CV risk factors, and
  disease
• Release stimulated by organ and vascular injury
• Participate in vascular repair (collateralization)
  and re-endothelialization, partly by paracrine
  effects
• Circulating numbers ?by exercise and drugs
  (statins and ACE inhibitors)
• Independent predictors of endothelial dysfunction
  and long-term prognosis in patients with CAD

Hill JM et al. N Engl J Med. 2003348593-600.
5
EPC number has prognostic importance
N 519 males with CAD, mean age 66 y
1.00
Group 3 (high EPC level)
0.98
0.96
Group 2 (medium EPC level)
Event-free survival
0.94
Group 1 (low EPC level)
0.92
0.90
0
100
200
300
365
0
Days
Werner N et al. N Engl J Med. 2005353999-1007.
6
Association between CV risk factors and EPC
colony counts
N 45 males without CAD, gt 21 years (mean age
50.3)
70
r 47.0 P 0.001
60
50
40
EPC colony-forming units
30
20
10
0
-5 0 5 10 15 20
Framingham risk score
Hill JM et al. N Engl J Med. 2003348593-600.
7
Mobilization of EPCs after myocardial infarction
N 16 patients with AMI, 8 controls
P lt 0.001 P lt 0.001
P lt 0.001 P lt 0.05
300
200
MNCCD34 (/106WBCs)
100
0
1 3 7 14 28
Day
Time after onset
Shintani S et al. Circulation. 20011032776-9.
8
VEGF levels correlate with increase in EPCs
450
r 0.35 P 0.01
400
350
300
250
200
MNCCD34 (cells/106 WBCs)
150
100
50
0
0
50
100
150
200
250
300
350
400
450
Plasma VEGF (pg/mL)
Shintani S et al. Circulation. 20011032776-9.
9
EPC activity and coronary collaterals

• 30 patients with isolated left anterior
  descending disease
• Divided into groups with (0.33) and without
  (0.09) adequate Collateral Flow Index (CFI)

B
R 0.75P lt 0.0001
0.8
0.6
CD34/CD133 Dual PositiveCells ( of total
lymphocytes)
0.4
0.2
0
0 0.1 0.2 0.3 0.4 0.5
CFI
Inadequate coronary collateral development
associated with numbers of circulating EPCs and
impaired chemotactic and pro-angiogenic activity
Lambiase PD et al. Circulation. 20041092986-92.
10
Decrease in EPCs associated with CV disease
Endothelial Progenitor Cells
Vasculoprotective agents
CV risk factors
Atherosclerosis
Disease Regression?
Disease Progression
Improvement of endothelial function Enhanced
re-endothelialization Reduced plaque
size Improved angiogenesis
Myocardial infarction Ischemic stroke Erectile
dysfunction Renal insufficiency Peripheral artery
disease
Werner N, Nickenig G. Arterioscler Thromb Vasc
Biol. 200626257-66.