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Although mortality rates from coronary heart disease in the western countries have declined in the last few decades, morbidity caused by this disease is increasing and a substantial number of patients still suffer acute coronary syndrome (ACS) and sudden cardiac death. Acute coronary syndrome occurs as a result of myocardial ischaemia and its manifestations(More)
Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstruct blood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable angina pectoris and the acute coronary(More)
Hyperhomocysteinemia is an independent risk factor for atherothrombosis. However, causality is unproven, and it remains unknown whether hyperhomocysteinemia promotes atherosclerosis, plaque rupture, and/or thrombosis. We evaluated the short- and long-term effects of hyperhomocysteinemia on plaque size and structure in 99 atherosclerosis-prone apolipoprotein(More)
OBJECTIVE Recent studies of bone marrow (BM)-transplanted apoE knockout (apoE-/-) mice have concluded that a substantial fraction of smooth muscle cells (SMCs) in atherosclerosis arise from circulating progenitor cells of hematopoietic origin. This pathway, however, remains controversial. In the present study, we reexamined the origin of plaque SMCs in(More)
Cardiovascular mortality is 10 to 20 times increased in patients with chronic renal failure (CRF). Risk factors for atherosclerosis are abundant in patients with CRF. However, the pathogenesis of cardiovascular disease in CRF remains to be elucidated. The effect of CRF on the development of atherosclerosis in apolipoprotein E-deficient male mice was(More)
Smooth muscle cells play a critical role in the development of atherosclerosis and its clinical complications. They were long thought to derive entirely from preexisting smooth muscle cells in the arterial wall, but this understanding has been challenged by the claim that circulating bone marrow-derived smooth muscle progenitor cells are an important source(More)
Coronary heart disease and ischaemic stroke caused by atherosclerosis are leading causes of illness and death worldwide. Small animal models have provided insight into the fundamental mechanisms driving early atherosclerosis, but it is increasingly clear that new strategies and research tools are needed to translate these discoveries into improved(More)
Mesenchymal stem cells (MSC) are defined as plastic-adherent, clonal cells that are common progenitors for osteoblasts and adipocytes. An inverse relationship between bone and fat has been observed in several clinical conditions and has been suggested to be caused by re-directing MSC differentiation into one particular lineage. However, this inverse(More)
Lack of animal models with human-like size and pathology hampers translational research in atherosclerosis. Mouse models are missing central features of human atherosclerosis and are too small for intravascular procedures and imaging. Modeling the disease in minipigs may overcome these limitations, but it has proven difficult to induce rapid atherosclerosis(More)
Circulating PCSK9 destines low-density lipoprotein receptor for degradation in lysosomes, resulting in increased LDL cholesterol. Accordingly, it is an attractive drug target for hypercholesterolemia, and results from clinical trials are promising. While the physiological role of PCSK9 in cholesterol metabolism is well described, its complex mechanism of(More)