Possible impact of electronegative LDL on atherosclerosis in type 2 diabetes

Tamura, Kouichi; Haruhara, Kotaro; Azushima, Kengo; Tokita, Yasuo; Wakui, Hiromichi

doi:10.1016/j.atherosclerosis.2017.08.018

Cited by 2 publications

(3 citation statements)

References 22 publications

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“…Thus, plasma L5 levels are increased in both patients with RA and those with SLE, thereby contributing to their accelerated atherosclerosis. Increased plasma L5 levels are also associated with an increased risk of ASCVD in patients with various other clinical diagnoses, including patients with uremia [ 43 ], ischemic peripheral arterial disease [ 44 ], or asymptomatic type 2 DM [ 39 , 40 ]. The risk of ASCVD in patients with asymptomatic type 2 DM is equivalent to that in patients with RA [ 88 ].…”

Section: Electronegative Ldl and Its Atherogenicitymentioning

confidence: 99%

“…Epidemiologic studies have shown increased morbidity and mortality rates due to ASCVD in patients with AIRDs [ 4 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 51 ], suggesting the importance of screening and preventive strategies for ASCVD, as well as its management. Although there is a paucity of consensus or randomized studies regarding therapeutic strategies for ASCVD in AIRDs, both the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) recommendations emphasize that patients with AIRDs should undergo risk factor monitoring, CVD risk modification, and dyslipidemia therapy, if needed [ 111 , 112 ].…”

Section: Proposed Therapeutic Strategies For Targeting Ascvd In Patients With Airdsmentioning

confidence: 99%

“…L5 and LDL (−) differ from native LDL in their physicochemical and biological characteristics, including size, density, lipid and protein composition, phospholipase activity, and apo B100 conformation [ 34 , 35 ]. Elevations in L5 or LDL (−) percentages in total LDL have been observed in patients with familial hypercholesterolemia [ 36 ], type 1 or type 2 diabetes mellitus (DM) [ 37 , 38 , 39 , 40 ], coronary artery disease [ 41 , 42 ], uremia [ 43 ], ischemic peripheral arterial disease [ 44 ], ST-elevation myocardial infarction (STEMI) [ 45 , 46 ], or acute ischemic stroke [ 47 ]. Furthermore, increases in the L5 percentage (i.e., L5%) and L5 levels are associated with the intensity of metabolic syndrome [ 48 ] and are speculated to be involved in the pathogenesis of ASCVD in patients with severe mental illness [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

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Autoimmune Rheumatic Diseases: An Update on the Role of Atherogenic Electronegative LDL and Potential Therapeutic Strategies

Chen

Sawamura

Dixon³

et al. 2021

JCM

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Atherosclerosis has been linked with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Autoimmune rheumatic diseases (AIRDs) are associated with accelerated atherosclerosis and ASCVD. However, the mechanisms underlying the high ASCVD burden in patients with AIRDs cannot be explained only by conventional risk factors despite disease-specific factors and chronic inflammation. Nevertheless, the normal levels of plasma low-density lipoprotein (LDL) cholesterol observed in most patients with AIRDs do not exclude the possibility of increased LDL atherogenicity. By using anion-exchange chromatography, human LDL can be divided into five increasingly electronegative subfractions, L1 to L5, or into electropositive and electronegative counterparts, LDL (+) and LDL (−). Electronegative L5 and LDL (−) have similar chemical compositions and can induce adverse inflammatory reactions in vascular cells. Notably, the percentage of L5 or LDL (−) in total LDL is increased in normolipidemic patients with AIRDs. Electronegative L5 and LDL (−) are not recognized by the normal LDL receptor but instead signal through the lectin-like oxidized LDL receptor 1 (LOX-1) to activate inflammasomes involving interleukin 1β (IL-1β). Here, we describe the detailed mechanisms of AIRD-related ASCVD mediated by L5 or LDL (−) and discuss the potential targeting of LOX-1 or IL-1β signaling as new therapeutic modalities for these diseases.

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