Table 1

Proposed Mechanisms for Stable IHD Syndromes

TypeLocation of DefectPotential Mechanisms
Coronary macrovesselsFlow-limiting stenosis (e.g., atherosclerosis)
Non–flow-limiting stenosis (e.g., atherosclerosis)
Endothelial dysfunction (e.g., athero RFs, viruses)
VSM dysfunction/spasm (e.g., athero RFs, ANS, drugs, viruses)
Thrombotic (e.g., hypercoagulation, enhanced platelet activation, plaque rupture/erosion/fissuring)
Embolic (e.g., AF, prosthetic valve, LV thrombus, SBE)
Inflammation (atherosclerosis, transplant, col dis [e.g., SLE, PAN, RA])
Congenital (muscle bridge, aberrant origin)
Dissection (e.g., pregnancy, chest trauma, Marfan)
Coronary microvesselsMicrovascular dysfunction (VSM dysfunction/spasm (e.g., athero RFs, ANS, viruses, drugs)
Endothelial dysfunction (e.g., athero RFs, viruses)
Endothelial cell-x cell “crosstalk” (e.g., EC-VSM, mononuclear cell, cardiomyocyte)
Microparticle occlusion (e.g., atheroma, cells, platelet microaggregation, cholesterol)
Thrombotic (e.g., hypercoagulable state, platelet activation, plaque rupture/erosion)
Microembolic (e.g., atheroma, AF, prosthetic valve, SBE)
Inflammation (athero, transplant, col dis [e.g., SLE, PAN, RA])
Capillary insufficiency (e.g., LVH)
Other vessels
 CapacitanceIncreased aortic-femoral arterial stiffness (e.g., aging, calcification, hypertension, CRI)
 TranscellularOxygen transport (reduced diffusion [e.g., infiltrate, amyloid])
Energy substrate (e.g., depleted FFA, glucose)
 IntracellularOxygen transport (e.g., defective myoglobin)
Energy substrate (e.g., depleted FFA, glucose)
 MitochondriaMitochondrial dysfunction/adaptation (ischemic injury/protection, HF, DM, aging)
Adventitia/matrixStroma-connective tissue proliferation
Adipocytes-estrogens (from androgens), leptins, and so on.
Leukocytes-cytokines, angiotensin II, and so on.
Mast cells, histamine, serotonin, proteoglycans, serine proteases, eicosanoids, and so on.
Sympathetic nerve activation
Vasa vasorum-capillary leak
OtherCNS dysfunction/disease, defective bone marrow-derived cells (e.g., CD34/CD133), T cells, among others.
Adipose-derived cells, among others.

AF = atrial fibrillation; ANS = autonomic nervous system; athero RF = atherosclerosis risk factors; CNS = central nervous system; col dis = collagen vascular disease; CRI = chronic renal insufficiency; DM = diabetes mellitus; EC = endothelial cell; FFA = free fatty-acid; HF = heart failure; IHD = ischemic heart disease; LV = left ventricular; LVH = left ventricular hypertrophy; PAN = polyarteritis nodosa; RA = rheumatoid arthritis; SBE = subacute bacterial endocarditis; SLE = systemic lupus erythematosus; VSM = vasomotor; ? = unknown.