Lower
limb peripheral artery disease (PAD) is poorly known by the general public and
even health care professionals. The manifestations of PAD are diverse depending
on the prevailing cardiovascular risk factors leading to the disease. Also the
outcome of patients is very different depending on the different manifestations
of the disease. The end-stage of PAD, known as critical limb ischemia (CLI), is
associated with very poor survival. In order to understand the heterogenic nature
of PAD in depth, different molecular mechanisms of the disease in association
with major cardiovascular risk factors and disease severity were investigated. The
findings indicate that different cardiovascular risk factors are associated with
diverse molecular pathology. This thesis work also shows that the presence of
crural atherosclerosis and CLI are tightly associated with poor patient survival,
and that especially CLI is associated with elevated levels of multiple circulating
cytokines, which resembles a systemic inflammatory condition. The major future
implications of the current findings are that CLI can no longer be referred to
as a plain condition of the lower limb and effort should be put into the attenuation
of the systemic inflammatory condition. Most importantly, the current findings
imply that future effort should be put into studying the risk factor specific
molecular mechanism leading to the disease in order to develop new specific
medical therapies according to the prevailing inflammatory pathology.