Arteriogenesis is promoted by flow- and pressure-related forces such as tangential wall stress and laminar shear stress. Exercise training (ET) is known to promote arteriogenesis in peripheral arterial disease (PAD) patients. It remains unclear whether supervised ET (SET) promotes arteriogenesis more efficiently than non-SET (nSET).
Methods and results
Forty PAD patients participated in a SET or nSET training programme (n = 20 each) and were compared to 20 healthy individuals without any history of cardiovascular events. Femoral artery diameter, flow and velocity were measured by ultrasound. Tangential wall stress and laminar shear stress were calculated for femoral arteries. Follow-up was performed after a mean of 7.65 ± 1.62 months. At follow-up, only the SET group showed a significant increase in lumen diameter of the profunda femoral artery (p = 0.03), accompanied by an increase of tangential wall stress (p = 0.002). Laminar shear stress decreased, but remained higher for the SET group compared to controls (p < 0.01). Individual changes in walking distance were higher for SET patients (p = 0.01) than nSET patients (p = 0.07). Profunda femoral lumen diameter and tangential wall stress correlated directly with walking distance (r = 0.446; p < 0.001), as well as with each other (r = 0.743; p < 0.0001).
Conclusions
Our results indicate that SET promotes arteriogenesis more efficiently than nSET. Femoral lumen diameter and flow might help with the monitoring of ET efficiency and potential arteriogenesis.
NorgrenLHiattWRDormandyJA. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg2007; 33(Suppl. 1): S1–S75.
2.
BhattDLStegPGOhmanEM. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA2006; 295: 180–189.
3.
HirschATHaskalZJHertzerNR. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation2006; 113: e463–e654.
4.
TenderaMAboyansVBartelinkML. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: The Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J2011; 32: 2851–2906.
5.
AndersonJLHalperinJLAlbertNM. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation2013; 127: 1425–1443.
6.
FokkenroodHJBendermacherBLLauretGJ. Supervised exercise therapy versus non-supervised exercise therapy for intermittent claudication. Cochrane Database Syst Rev2013; 8: CD005263–CD005263.
7.
NiessnerARichterBPenkaM. Endurance training reduces circulating inflammatory markers in persons at risk of coronary events: impact on plaque stabilization?Atherosclerosis2006; 186: 160–165.
8.
TimmermanKLFlynnMGCoenPM. Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: A role in the anti-inflammatory influence of exercise?J Leukoc Biol2008; 84: 1271–1278.
9.
MichishitaRShonoNInoueT. Effect of exercise therapy on monocyte and neutrophil counts in overweight women. Am J Med Sci2010; 339: 152–156.
10.
HigashiYSasakiSKurisuS. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: Role of endothelium-derived nitric oxide. Circulation1999; 100: 1194–1202.
11.
HigashiYSasakiSSasakiN. Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension. Hypertension1999; 33: 591–597.
12.
GotoCHigashiYKimuraM. Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: Role of endothelium-dependent nitric oxide and oxidative stress. Circulation2003; 108: 530–535.
13.
RisauW. Mechanisms of angiogenesis. Nature1997; 386: 671–674.
14.
SchaperW. On arteriogenesis – A reply. Basic Res Cardiol2003; 98: 183–184.
15.
HeilMEitenmullerISchmitz-RixenT. Arteriogenesis versus angiogenesis: Similarities and differences. J Cell Mol Med2006; 10: 45–55.
16.
Ben DrissABenessianoJPoitevinP. Arterial expansive remodeling induced by high flow rates. Am J Physiol1997; 272: H851–H858.
17.
HuonkerMHalleMKeulJ. Structural and functional adaptations of the cardiovascular system by training. Int J Sports Med1996; 17(Suppl. 3): S164–S172.
18.
NashMSMontalvoBMApplegateB. Lower extremity blood flow and responses to occlusion ischemia differ in exercise-trained and sedentary tetraplegic persons. Arch Phys Med Rehabil1996; 77: 1260–1265.
19.
GardnerAWPoehlmanET. Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis. JAMA1995; 274: 975–980.
20.
de SimoneGDevereuxRBChienS. Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults. Circulation1990; 81: 107–117.
21.
OstadMAEggelingSTschentscherP. Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: Results of the CEZAR study. Atherosclerosis2009; 205: 227–232.
22.
GoriTDragoniSLisiM. Conduit artery constriction mediated by low flow a novel noninvasive method for the assessment of vascular function. J Am Coll Cardiol2008; 51: 1953–1958.
23.
HaasTLLloydPGYangHT. Exercise training and peripheral arterial disease. Compr Physiol2012; 2: 2933–3017.
24.
KamiyaATogawaT. Adaptive regulation of wall shear stress to flow change in the canine carotid artery. Am J Physiol1980; 239: H14–H21.
25.
TroncFWassefMEspositoB. Role of NO in flow-induced remodeling of the rabbit common carotid artery. Arterioscler Thromb Vasc Biol1996; 16: 1256–1262.
26.
WijnenJAKuipersHKoolMJ. Vessel wall properties of large arteries in trained and sedentary subjects. Basic Res Cardiol1991; 86(Suppl. 1): 25–29.
27.
DinennoFATanakaHMonahanKD. Regular endurance exercise induces expansive arterial remodelling in the trained limbs of healthy men. J Physiol2001; 534: 287–295.
28.
HeilMSchaperW. Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res2004; 95: 449–458.
29.
HelischASchaperW. Arteriogenesis: The development and growth of collateral arteries. Microcirculation2003; 10: 83–97.
UnthankJLNixonJCDalsingMC. Inhibition of NO synthase prevents acute collateral artery dilation in the rat hindlimb. J Surg Res1996; 61: 463–468.
32.
DemichevaEHeckerMKorffT. Stretch-induced activation of the transcription factor activator protein-1 controls monocyte chemoattractant protein-1 expression during arteriogenesis. Circ Res2008; 103: 477–484.
33.
CornelissenVAOnkelinxSGoetschalckxK. Exercise-based cardiac rehabilitation improves endothelial function assessed by flow-mediated dilation but not by pulse amplitude tonometry. Eur J Prev Cardiol2014; 21: 39–48.
34.
SandriMViehmannMAdamsV. Chronic heart failure and aging – Effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig Exercise Intervention in Chronic heart failure and Aging (LEICA) study. Eur J Prev Cardiol2016; 23: 349–358.
35.
Siasos G, Athanasiou D, Terzis G, et al. Acute effects of different types of aerobic exercise on endothelial function and arterial stiffness. Eur J Prev Cardiol. 23: 1565–1572.
36.
DopheideJFDopplerCScheerM. Critical limb ischaemia is characterised by an increased production of whole blood reactive oxygen species and expression of TREM-1 on neutrophils. Atherosclerosis2013; 229: 396–403.
37.
SchaperW. Tangential wall stress as a molding force in the development of collateral vessels in the canine heart. Experientia1967; 23: 595–596.
38.
LaufsULa FataVPlutzkyJ. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation1998; 97: 1129–1135.
39.
LaufsUUrhausenAWernerN. Running exercise of different duration and intensity: Effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil2005; 12: 407–414.
40.
LaufsUWernerNLinkA. Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation2004; 109: 220–226.
41.
ItoWDArrasMWinklerB. Monocyte chemotactic protein-1 increases collateral and peripheral conductance after femoral artery occlusion. Circ Res1997; 80: 829–837.
42.
UrbichCAicherAHeeschenC. Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol2005; 39: 733–742.
43.
BrehmWWagnerPSyguschR. Health promotion by means of health sport – A framework and a controlled intervention study with sedentary adults. Scand J Med Sci Sports2005; 15: 13–20.
