Human HDL containing a novel apoC-I isoform induces smooth muscle cell apoptosis

Abstract

Some HDL subclasses enriched in a novel isoform of apoC-I induce extensive ASMC apoptosis in vitro. Individuals with this apoptotic HDL phenotype generally have higher apoC-I and HDL-C levels consistent with an inhibitory effect of apoC-I on cholesteryl ester transfer protein activity. The association of this phenotype with processes that can promote plaque rupture may explain a source of CHD risk not accounted for by the classical risk factors.

Apolipoprotein Proteomic Profiling for the Prediction of Cardiovascular Death in Patients with Heart Failure

“…Apo-C1 and its truncated form (Apo-C1 des Thr-Pro N-Term) have been previously associated with apoptosis of human aortic smooth muscle cell in vitro. [10] Recently, Roura et al [13] have shown that plasma-derived extracellular vesicles obtained from patients with dilated cardiomyopathy contained more Apo-C1 as compared to healthy control patients. To our knowledge, this is the first time that circulating levels of Apo-C1 are related to cardiovascular death (lower in patients alive after three years of HF evaluation) in HF patients.…”

“…Beside their role in atherosclerosis, numerous Apo have been implicated in several other physiopathological mechanisms, which have been shown to be implicated in HF worsening and left ventricle remodeling such as inflammation, oxidative stress, fibrosis, and apoptosis. [9,10,24,25] Of note, Amin et al reported that selective Apo-A1 gene transfer is able to counteract cardiac hypertrophy, reduce myocardial fibrosis, and improve cardiac function in a model of mice with chronic pressure overload by www.advancedsciencenews.com www.clinical.proteomics-journal.com transverse aortic constriction. [9] More recently, Deleon-Pennell et al found, using a glycoproteomic profiling, that Apo-F is independently associated with the risk of later progression to HF after myocardial infarction in humans.…”

“…Recently, besides their role in atherosclerosis and the subsequent ischemic cardiomyopathy, several apolipoproteins (Apo) have been implicated in physiopathological mechanisms (involved in HF progression and left ventricle remodeling) such as inflammation, oxidative stress, fibrosis, and apoptosis. [9,10] Several studies involving Apo profiling with several technologies such as electroimmunoassays [11] or MS [12] have shown associations of very low density lipoprotein (VLDL)-associated Apo with incident cardiovascular disease (CVD) in the general community [12] and that Apo-C3 in total serum and in high density…”

Diagnostic and prognostic significance of serum apolipoprotein C-I in triple-negative breast cancer based on mass spectrometry

“…Moreover, inhibition of apoC-I with short interfering RNA suppressed proliferation and induced apoptosis of pancreatic cancer cells, indicating that apoC-I contributes to the aggressive nature of pancreatic cancer through avoidance of spontaneous apoptotic cell death and should therefore serve as a useful novel therapeutic target. ApoC-I has additionally been reported to promote human aortic smooth muscle cell apoptosis by stimulating expression of caspase-3, a crucial executioner in the pathway leading to DNA fragmentation and apoptosis, 71,72 and identified as a putative BC biomarker using proteomic techniques, including SELDI-TOF-MS, MALDI-TOF/TOF-MS, isobaric tags for relative and absolute quantification (iTRAQ) and 2-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS). 57,73 However, in addition to systematic bias by pre-analytical parameters, these earlier reports employed MALDI-based screening and did not verify the results obtained with PCR-and immunoassay-based assays.…”

Proteogenomic review of the changes in primate apoC-I during evolution

“…As noted in section B-2, Herbert et al noted in their studies that the cynomalgous monkey had a similar truncated form as well (28). A novel variation in apoC-I mass has recently been reported in certain patients suffering from coronary heart disease (35). However, it still remains to be determined whether the mass increase of 89 Da is due to a mutation, post-translational modification or a combination of both.…”