Mechanisms Underlying Arterial Fragility and the Complications of Atherosclerosis

Abstract

The etiology of atherosclerosis must explain the development of primary pathological complications (intimal tears, ectasia, tortuosity, aneurysms and stenoses). They are interrelated and associated with destruction of mural architecture and concomitant loss of tensile strength (fragility) attributable to bioengineering fatigue. The complications become manifested clinically by ischemia, hemorrhage and pressure effects developing with greater frequency in association with hypertension, arteriovenous shunts or connective tissue disorders. Moreover they are produced experimentally and iatrogenically by hemodynamic means but are unexplained by other current etiological hypotheses.

Identification of two susceptibility loci for vascular fragility in the Brown Norway rat

“…As well as the iliac, femoral, and carotid bifurcations, the distal abdominal aorta appears particularly vulnerable to IEL defect formation. Although there is controversy as to the nature of elastic tissue damage in atherosclerosis and AAA (40), there is clear evidence that biophysical fatigue is at least one factor (39). Disruption of the IEL is by no means unique to human and rat arteries and has been reported within the arteries of numerous vertebrates, including reptiles (9).…”

Observations on the Development of Mural Thrombi in Chronic Experimental Aneurysms in Sheep

“…Aneurysmal enlargement and rupture are attributable to progressive weakening and bioengineering fatigue of mural constituents due to the characteristically augmented pulsatile, distensile stresses that are aggravated by high pulse pressures and vibratory stresses of lesser amplitude within the sac (18)(19)(20). In cerebral aneurysms the pulsatile increase in volume amounts to 5 1 t I07o with an increase of 1-1 .5 mm in at least one diameter (21) which is substantial for such small sacs.…”

Increased bleeding risk during percutaneous coronary interventions by arterial hypertension

“…The existence of unknown risk factors or comorbidities among patients with arterial hypertension cannot not be excluded. Furthermore, increased vascular fragility and vascular lesions caused by chronic hypertension and effects exerted by elevated blood pressure at the time of PCI may be suggested as factors that may increase the risk of bleeding in patients with arterial hypertension.…”

“…Although explanation of this finding may be incomplete, some evidence seems to support it. Vascular complications of atherosclerosis such as intimal tears, vessel ectasia, tortuosity, or aneurisms are aggravated and become clinically manifested (including bleeding) with a greater frequency by arterial hypertension . The antiaggregant/anticoagulant therapy used during PCI procedures may facilitate bleeding by attenuating the protective role of blood coagulation at the sites of vascular alterations.…”