Thrombotic and cardiovascular risks in type two diabetes; Role of platelet hyperactivity

Gaiz, Almottesembellah; Mosawy, Sapha; Colson, Natalie Jane; Singh, Indu

doi:10.1016/j.biopha.2017.07.121

Cited by 57 publications

(44 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In diabetes, several factors including impaired fibrinolysis, increased coagulation, endothelial dysfunction and platelet hyperreactivity, contribute to the prothombic condition that describes patients with T2DM [7, 13, 15, 16, 49, 149, 150]. Platelets are characterized to be hyperactive with increased activation, adhesion and aggregation due to dysregulation of several signaling pathways in T2DM patients [7, 13–16, 151].…”

Section: Platelets Hyperactivity In T2dmmentioning

confidence: 99%

“…Platelets are characterized to be hyperactive with increased activation, adhesion and aggregation due to dysregulation of several signaling pathways in T2DM patients [7, 13–16, 151]. Platelets involve in disease pathology by not only triggering thrombus formation but also by releasing oxidative, mitogenic and vasoconstrictive substances that induce the development of local vascular lesions.…”

Section: Platelets Hyperactivity In T2dmmentioning

confidence: 99%

“…These changes further impair vasorelaxation and increase proliferation of vascular smooth muscle cells [12]. Along with other contributors of prothrombotic state in T2DM, platelet dysfunction plays a pivotal role [13]. Activation of endothelium by increased release of cytokines and expression of adhesion molecules mediates platelet activation and adhesion to activated endothelium [13–16].…”

Section: Introductionmentioning

confidence: 99%

“…Along with other contributors of prothrombotic state in T2DM, platelet dysfunction plays a pivotal role [13]. Activation of endothelium by increased release of cytokines and expression of adhesion molecules mediates platelet activation and adhesion to activated endothelium [13–16]. Impaired endogenous inhibition of platelets makes platelets more susceptible to activation and activated endothelium provides more adhesion molecules and platelet agonists.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, after firm adhesion to activated endothelium, leukocyte transmigrates and presents to lipid and cells in vessel wall. This accelerates the further inflammatory reactions in the vascular wall and promotes atherosclerotic vascular complications [13–16]. Therefore, understanding of mechanism of endothelial and platelet dysfunction, unquestionably involved in pathogenesis of T2DM, is required to ameliorate the adverse vascular events, leading to prothrombotic state in T2DM.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies

Kaur

Singh

2018

Cardiovasc Diabetol

494

363

View full text Add to dashboard Cite

The incidence and prevalence of diabetes mellitus is rapidly increasing worldwide at an alarming rate. Type 2 diabetes mellitus (T2DM) is the most prevalent form of diabetes, accounting for approximately 90–95% of the total diabetes cases worldwide. Besides affecting the ability of body to use glucose, it is associated with micro-vascular and macro-vascular complications. Augmented atherosclerosis is documented to be the key factor leading to vascular complications in T2DM patients. The metabolic milieu of T2DM, including insulin resistance, hyperglycemia and release of excess free fatty acids, along with other metabolic abnormalities affects vascular wall by a series of events including endothelial dysfunction, platelet hyperactivity, oxidative stress and low-grade inflammation. Activation of these events further enhances vasoconstriction and promotes thrombus formation, ultimately resulting in the development of atherosclerosis. All these evidences are supported by the clinical trials reporting the importance of endothelial dysfunction and platelet hyperactivity in the pathogenesis of atherosclerotic vascular complications. In this review, an attempt has been made to comprehensively compile updated information available in context of endothelial and platelet dysfunction in T2DM.

show abstract

Section: Platelets Hyperactivity In T2dmmentioning

confidence: 99%

Section: Platelets Hyperactivity In T2dmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies

Kaur

Singh

2018

Cardiovasc Diabetol

494

363

View full text Add to dashboard Cite

show abstract

Endothelial dysfunction and cardiovascular outcome in asymptomatic patients with type 2 diabetes: A pilot study

Villano

Mencarelli

Melita

et al. 2019

Diabetes Metabolism Res

View full text Add to dashboard Cite

BackgroundType 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events, but risk stratification of asymptomatic T2DM patients remains a challenging issue. We conducted a pilot study to assess whether endothelial dysfunction might help identify, among asymptomatic T2DM patients, those at increased risk of cardiovascular events.MethodsWe studied 61 consecutive T2DM patients with no evidence of cardiovascular disease and no insulin therapy. Endothelial function was assessed by flow‐mediated dilation (FMD) of the right brachial artery. The primary endpoint was a combination of major cardiovascular events (MACE: cardiovascular death, acute coronary events, coronary interventions, and acute cerebrovascular accidents). FMD was repeated at follow‐up in 48 patients (79%).ResultsA total of 10 MACE (16.4%) occurred during a mean follow‐up of 48 months, including three acute myocardial infarctions, five coronary revascularizations for stable angina, and two acute ischaemic strokes. FMD at enrolment was lower in patients with compared with patients without MACE (3.78 ± 0.97% vs 4.70 ± 1.33%, respectively; P = .04). No other clinical or laboratory variables (age, diabetes duration, glycated haemoglobin, cardiovascular risk factors, drug therapy, and nitrate‐mediated dilation) were associated with MACE. FMD at follow‐up was also lower in patients with (n = 10) compared with those without (n = 38) MACE (3.66 ± 1.29 vs 4.85 ± 1.92; P = .006).ConclusionsOur data suggest that assessment of FMD might be helpful to identify patients at increased risk of MACE among individuals with asymptomatic T2DM; accordingly, a large study is warranted to adequately define the clinical utility of FMD assessment in the management of T2DM patients.

show abstract

The degenerative impact of hyperglycemia on the structure and mechanics of developing murine intervertebral discs

et al. 2022

View full text Add to dashboard Cite

Introduction: Diabetes has long been implicated as a major risk factor for intervertebral disc (IVD) degeneration, interfering with molecular signaling and matrix biochemistry, which ultimately aggravates the progression of the disease. Glucose content has been previously shown to influence structural and compositional changes in engineered discs in vitro, impeding fiber formation and mechanical stability.Methods: In this study, we investigated the impact of diabetic hyperglycemia on young IVDs by assessing biochemical composition, collagen fiber architecture, and mechanical behavior of discs harvested from 3-to 4-month-old db/db mouse caudal spines.Results: We found that discs taken from diabetic mice with elevated blood glucose levels demonstrated an increase in total glycosaminoglycan and collagen content, but comparable advanced glycation end products (AGE) levels to wild-type discs. Diabetic discs also contained ill-defined boundaries between the nucleus pulposus and annulus fibrosus, with the latter showing a disorganized and unaligned collagen fiber network at this same boundary.Conclusions: These compositional and structural changes had a detrimental effect on function, as the diabetic discs were twice as stiff as their wild-type counterparts and demonstrated a significant resistance to deformation. These results indicate that diabetes may predispose the young disc to DDD later in life by altering patterns of extracellular matrix deposition, fiber formation, and motion segment mechanics independently of AGE accumulation.

show abstract

Thrombotic and cardiovascular risks in type two diabetes; Role of platelet hyperactivity

Cited by 57 publications

References 64 publications

Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies

Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies

Endothelial dysfunction and cardiovascular outcome in asymptomatic patients with type 2 diabetes: A pilot study

The degenerative impact of hyperglycemia on the structure and mechanics of developing murine intervertebral discs

Contact Info

Product

Resources

About