Atherothrombotic Vascular Disease Research Articles

Dyslipoproteinemias in postmenopausal women and new therapeutic targets

Dyslipoproteinemias play a very prominent role in the pathogenesis of atherosclerosis in postmenopausal women; These lose the cardiovascular protection of estrogens, increasing the risk of developing atherothrombotic vascular disease (CVD). International guidelines do not vary between the management of dyslipidemia between men and women, but these are treated less vigorously and without taking into account the postmenopausal hormonal situation. Its management must be included in the individual risk of each woman, with the new LDL goals and above all take into account Lipoproteins rich in Triglycerides (LPRTG) that are associated with the classic modifiable risk factors, in a non-modifiable biological terrain such as are age and genetic family history; which may be associated with emerging factors such as Lipoprotein “a” (Lp a), hyperhomocysteine, elevated CRP (C-reactive protein), among other factors that are rarely taken into account. Statins demonstrated their effectiveness in reducing LDL and even increasing HDL, reducing cardio and cerebrovascular events, but a good percentage of patients, despite the intensified doses, remain at Residual Lipid Risk, so we must resort to new therapeutic targets. like biological ones.

P2Y12 Receptor Inhibitor for Antiaggregant Therapies: From Molecular Pathway to Clinical Application.

Platelets play a significant role in hemostasis, forming plugs at sites of vascular injury to limit blood loss. However, if platelet activation is not controlled, it can lead to thrombotic events, such as myocardial infarction and stroke. To prevent this, antiplatelet agents are used in clinical settings to limit platelet activation in patients at risk of arterial thrombotic events. However, their use can be associated with a significant risk of bleeding. An enhanced comprehension of platelet signaling mechanisms should facilitate the identification of safer targets for antiplatelet therapy. Over the past decade, our comprehension of the breadth and intricacy of signaling pathways that orchestrate platelet activation has expanded exponentially. Several recent studies have provided further insight into the regulation of platelet signaling events and identified novel targets against which to develop novel antiplatelet agents. Antiplatelet drugs are essential in managing atherothrombotic vascular disease. The current antiplatelet therapy in clinical practice is limited in terms of safety and efficacy. Novel compounds have been developed in response to patient variability and resistance to aspirin and/or clopidogrel. Recent studies based on randomized controlled trials and systematic reviews have definitively demonstrated the role of antiplatelet therapy in reducing the risk of cardiovascular events. Antiplatelet therapy is the recommended course of action for patients with established atherosclerosis. These studies compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. However, in patients undergoing percutaneous coronary intervention, it is still unclear whether the efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy depends on the type of P2Y12 inhibitor. This paper focuses on the advanced-stage evaluation of several promising antiplatelet drugs.

Melatonin ameliorates myocardial infarction in obese diabetic individuals: The possible involvement of macrophage apoptotic factors.

In recent days, the hike in obesity-mediated epidemics across the globe and the prevalence of obesity-induced cardiovascular diseasehas become one of the chief grounds for morbidity and mortality. This epidemic-driven detrimental events in the cardiac tissues start with the altered distribution and metabolism pattern of high-density lipoproteinand low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on the arterial wall and atherosclerotic plaque generation, followed by vascular spasms and infarction. Subsequently, obesity-triggered metabolic malfunctions induce free radical generation which may further trigger pro-inflammatory signaling and nuclear factor kappa-light-chain-enhancer of activated B cellstranscriptional factor, thus inducing interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase. This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby makingobese diabetic patients prone towardthe development of myocardial infarction (MI) or stroke in comparison to their nondiabetic counterparts. The accelerated oxidative stress and pro-inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals, causing progression of athero-thrombotic vascular disease. Being an efficient antioxidative and anti-inflammatory indolamine, melatonin effectively inhibits lipid peroxidation, pro-inflammatory reactions, thereby resolving free radical-induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterolconcentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti-inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity-induced acute MI. This review aimed at orchestrating the efficacy of melatonin in ameliorating irrevocable oxidative cardiovascular damage induced by the obesity-diabetes correlation.

Statins and Inflammation.

Chronic inflammation has been recognized as one of the most important pathophysiological mechanisms' initiation and progression of atherosclerosis. Statins belong to most successful therapeutic agents in the prevention and treatment of atherothrombotic vascular disease. Their non-lipid related effects including suppression of inflammation have been repeatedly proven in both experimental and clinical settings. Recently, the importance of inflammation in the process of atherosclerosis has been confirmed by interventions targeting inflammation selectively. Clinical trial with selective inhibitor of a principal inflammatory mediator interleukin 1-beta - canakinumab - confirmed the notion of direct vasculoprotective effects of primarily targeting inflammation. This has increased interest in the non-lipid, pleiotropic and, particularly, anti-inflammatory effects of statins. Anti-inflammatory effects of statins have been proven both experimentally and in clinical settings beyond any doubt. They comprise a direct positive effect on not only many cell types and pathways that are lipid independent but, also, some that are mediated by lipid modification. Undoubtedly, suppression of inflammatory response by statins contributes to their generally positive action in atherosclerosis and represents an important part of the vasculo- and atheroprotective effect of this drug class.

K-80003 Inhibition of Macrophage Apoptosis and Necrotic Core Development in Atherosclerotic Vulnerable Plaques

PurposeMacrophage apoptosis coupled with a defective phagocytic clearance of the apoptotic cells promotes plaque necrosis in advanced atherosclerosis, which causes acute atherothrombotic vascular disease. Nonsteroidal anti-inflammatory drug sulindac derivative K-80003 treatment was previously reported to dramatically attenuate atherosclerotic plaque progression and destabilization. However, the underlying mechanisms are not fully understood. This study aimed to determine the role of K-80003 on macrophage apoptosis and elucidate the underlying mechanism.MethodsThe mouse model of vulnerable carotid plaque in ApoE−/− mice was developed in vivo. Consequently, mice were randomly grouped into two study groups: the control group and the K-80003 group (30 mg/kg/day). Samples of carotid arteries were collected to determine atherosclerotic necrotic core area, cellular apoptosis, and oxidative stress. The effects of K-80003 on RAW264.7 macrophage apoptosis, oxidative stress, and autophagic flux were also examined in vitro.ResultsK-80003 significantly suppressed necrotic core formation and inhibited cellular apoptosis of vulnerable plaques. K-80003 can also inhibit 7-ketocholesterol-induced macrophage apoptosis in vitro. Furthermore, K-80003 inhibited intraplaque cellular apoptosis mainly through the suppression of oxidative stress, which is a key cause of advanced lesional macrophage apoptosis. Mechanistically, K-80003 prevented 7-ketocholesterol-induced impairment of autophagic flux in macrophages, evidenced by the decreased LC3II and SQSTM1/p62 expression, GFP-RFP-LC3 cancellation upon K-80003 treatment.ConclusionInhibition of macrophage apoptosis and necrotic core formation by autophagy-mediated reduction of oxidative stress is one mechanism of the suppression of plaque progression and destabilization by K-80003.

Macrophage autophagy regulates mitochondria-mediated apoptosis and inhibits necrotic core formation in vulnerable plaques.

The vulnerable plaque is a key distinguishing feature of atherosclerotic lesions that can cause acute atherothrombotic vascular disease. This study was designed to explore the effect of autophagy on mitochondria‐mediated macrophage apoptosis and vulnerable plaques. Here, we generated the mouse model of vulnerable carotid plaque in ApoE−/− mice. Application of ApoE−/− mice with rapamycin (an autophagy inducer) inhibited necrotic core formation in vulnerable plaques by decreasing macrophage apoptosis. However, 3‐methyladenine (an autophagy inhibitor) promoted plaque vulnerability through deteriorating these indexes. To further explore the mechanism of autophagy on macrophage apoptosis, we used macrophage apoptosis model in vitro and found that 7‐ketocholesterol (7‐KC, one of the primary oxysterols in oxLDL) caused macrophage apoptosis with concomitant impairment of mitochondria, characterized by the impairment of mitochondrial ultrastructure, cytochrome c release, mitochondrial potential dissipation, mitochondrial fragmentation, excessive ROS generation and both caspase‐9 and caspase‐3 activation. Interestingly, such mitochondrial apoptotic responses were ameliorated by autophagy activator, but exacerbated by autophagy inhibitor. Finally, we found that MAPK‐NF‐κB signalling pathway was involved in autophagy modulation of 7‐KC–induced macrophage apoptosis. So, we provide strong evidence for the potential therapeutic benefit of macrophage autophagy in regulating mitochondria‐mediated apoptosis and inhibiting necrotic core formation in vulnerable plaques.

Impact of Lifestyle Interventions Targeting Healthy Diet, Physical Activity, and Weight Loss on Asthma in Adults: What Is the Evidence?

Unhealthy lifestyle factors such as poor diet quality, sedentary lifestyle, and obesity are associated with negative health consequences in asthma including poor asthma control, impaired quality of life, and greater health care utilization. Lifestyle modification is the cornerstone of behavioral treatments and has been effective in chronic diseases such as atherothrombotic vascular disease and diabetes. There is a critical need for lifestyle interventions in asthma care that address obesity and its intimately linked risk behaviors in terms of poor diet and physical inactivity. We present in this commentary the promising lifestyle interventions emerging in asthma care that target poor diet, physical inactivity and weight loss, the proposed mechanisms of these lifestyle interventions, and the critical need for guideline-concordant lifestyle interventions in asthma care.

MerTK receptor cleavage promotes plaque necrosis and defective resolution in atherosclerosis.

Atherothrombotic vascular disease is often triggered by a distinct type of atherosclerotic lesion that displays features of impaired inflammation resolution, notably a necrotic core and thinning of a protective fibrous cap that overlies the core. A key cause of plaque necrosis is defective clearance of apoptotic cells, or efferocytosis, by lesional macrophages, but the mechanisms underlying defective efferocytosis and its possible links to impaired resolution in atherosclerosis are incompletely understood. Here, we provide evidence that proteolytic cleavage of the macrophage efferocytosis receptor c-Mer tyrosine kinase (MerTK) reduces efferocytosis and promotes plaque necrosis and defective resolution. In human carotid plaques, MerTK cleavage correlated with plaque necrosis and the presence of ischemic symptoms. Moreover, in fat-fed LDL receptor-deficient (Ldlr-/-) mice whose myeloid cells expressed a cleavage-resistant variant of MerTK, atherosclerotic lesions exhibited higher macrophage MerTK, lower levels of the cleavage product soluble Mer, improved efferocytosis, smaller necrotic cores, thicker fibrous caps, and increased ratio of proresolving versus proinflammatory lipid mediators. These findings provide a plausible molecular-cellular mechanism that contributes to defective efferocytosis, plaque necrosis, and impaired resolution during the progression of atherosclerosis.

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come.

Protease receptor antagonism to target blood platelet therapies.

Platelet activation and thrombus formation play a central role in ischemic vascular disease. Thrombin, an especially potent physiologic agonist mediating in vivo activation of platelets, acts via a unique family of G-protein-coupled receptors called protease-activated receptors (PARs) with a broad tissue expression. This review focuses on current antiplatelet therapies as well as innovative approaches to targeting PARs in patients with atherothrombotic vascular disease.

American Heart Association Cardiovascular Genome-Phenome Study: foundational basis and program.

The American Heart Association has established the Cardiovascular Genome-Phenome Study (CV-GPS) as a means by which to achieve the goal of using modern genomics and phenotyping optimally to combat cardiovascular disease (CVD). CVD remains the leading cause of death in the United States and has become a major cause of morbidity and mortality worldwide. The course of CVD begins at an early age and evolves throughout life. Typically, risk factor precursors (eg, prehypertension, borderline abnormal lipids) are first observed in adolescence or young adulthood. By middle age, they develop into full-fledged cardiometabolic risk factors and subclinical disease, which usually become clinically apparent in older age. Importantly, risk factors for CVD reflect the complex interplay between genetic and environmental factors and demonstrate the complexity of the multiple determinants of disease. Editorial see p 17 Many of the genetic and environmental determinants of CVD have been identified over the past 50 years, and successful preventive and therapeutic strategies have been developed as a result. However, many potential genetic or acquired disease drivers remain unaccounted for, as illustrated by the observation that the major CVD risk factors combined account for only a fraction of the population-attributable risk.1 In addition, variations in CVD risk exist among individuals with similar risk profiles. Part of these differences may reflect differences in profiles of known risk factors that have not yet been fully refined but also individual differences in underlying genetic modifiers of such risk factors. Modern genomics, with its ability to provide ideally unbiased analysis of the entire genome, offers an approach to the ascertainment of all genetic determinants of CVD. Furthermore, the increasingly broad range of “omics” methods, including RNA-Seq, modern proteomics, metabolomics, and metabonomics, provide deeper and more refined molecular detail by which to define an individual’s genome and its relationship to (patho)phenotype. …

Comparison of telomere length in black and white teachers from South Africa: the sympathetic activity and ambulatory blood pressure in Africans study.

Telomere length is a marker of biological aging that has been linked to cardiovascular disease risk. The black South African population is witnessing a tremendous increase in the prevalence of cardiovascular disease, part of which might be explained through urbanization. We compared telomere length between black South Africans and white South Africans and examined which biological and psychosocial variables played a role in ethnic difference in telomere length. We measured leukocyte telomere length in 161 black South African teachers and 180 white South African teachers aged 23 to 66 years without a history of atherothrombotic vascular disease. Age, sex, years having lived in the area, human immunodeficiency virus (HIV) infection, hypertension, body mass index, dyslipidemia, hemoglobin A1c, C-reactive protein, smoking, physical activity, alcohol abuse, depressive symptoms, psychological distress, and work stress were considered as covariates. Black participants had shorter (median, interquartile range) relative telomere length (0.79, 0.70-0.95) than did white participants (1.06, 0.87-1.21; p < .001), and this difference changed very little after adjusting for covariates. In fully adjusted models, age (p < .001), male sex (p = .011), and HIV positive status (p = .023) were associated with shorter telomere length. Ethnicity did not significantly interact with any covariates in determining telomere length, including psychosocial characteristics. Black South Africans showed markedly shorter telomeres than did white South African counterparts. Age, male sex, and HIV status were associated with shorter telomere length. No interactions between ethnicity and biomedical or psychosocial factors were found. Ethnic difference in telomere length might primarily be explained by genetic factors.

HDL and atherothrombotic vascular disease.

High-density lipoproteins (HDLs) exert many beneficial effects which may help to protect against the development or progression of atherosclerosis or even facilitate lesion regression. These activities include promoting cellular cholesterol efflux, protecting low-density lipoproteins (LDLs) from modification, preserving endothelial function, as well as anti-inflammatory and antithrombotic effects. However, questions remain about the relative importance of these activities for atheroprotection. Furthermore, the many molecules (both lipids and proteins) associated with HDLs exert both distinct and overlapping activities, which may be compromised by inflammatory conditions, resulting in either loss of function or even gain of dysfunction. This complexity of HDL functionality has so far precluded elucidation of distinct structure-function relationships for HDL or its components. A better understanding of HDL metabolism and structure-function relationships is therefore crucial to exploit HDLs and its associated components and cellular pathways as potential targets for anti-atherosclerotic therapies and diagnostic markers.

Influence of Dietary Saturated Fat Intake on Endothelial Fibrinolytic Capacity in Adults

Approximately 50% of middle-aged and older adults in the United States regularly consume a diet high in saturated fat. High dietary saturated fat intake has been linked to promote atherothrombotic vascular disease. We tested the hypothesis that endothelial fibrinolytic function is diminished in middle-aged and older adults who habitually consume a diet high in saturated fat. Twenty-four healthy, sedentary middle-aged, and older adults (54 to 71years) were studied: 10 (8 men and 2 women) with a dietary saturated fat intake <10% (lower saturated fat) of total calories and 14 (9 men and 5 women) with a dietary saturated fat intake ≥10% of total calories (high saturated fat). Net endothelial release of tissue-type plasminogen activator (t-PA), the primary activator of fibrinolysis, was determined, invivo, in response to intrabrachial infusions of bradykinin (12.5 to 50.0ng/100ml tissue/min) and sodium nitroprusside (1.0 to 4.0μg/100ml tissue/min). Capacity of the endothelium to release t-PA in response to bradykinin was ∼30% less (p <0.05) in the high (from-0.7 ± 0.6 to 36.9 ± 3.3ng/100ml tissue/min) compared with the lower (from-0.3 ± 0.3 to 53.4 ± 7.8ng/100ml tissue/min) dietary saturated fat group. Moreover, total amount of t-PA released was significantly less (∼30%) (201 ± 22 vs 274 ± 29ng/100ml tissue) in the adults who reported consuming a diet high in saturated fat. These results indicate that the capacity of the endothelium to release t-PA is lower in middle-aged and older adults who habitually consume a diet high in saturated fat. In conclusion, endothelial fibrinolytic dysfunction may underlie the increased atherothrombotic disease risk with a diet high in saturated fat.

Dietary manipulation of platelet function.

Activated platelets contribute to plaque formation within blood vessels in the early and late stages of atherogenesis, and therefore they have been proposed as risk factor for cardiovascular disease. Anti-platelet drugs, such as aspirin, are now the most prescribed pharmacological treatment in Europe. Certain dietary bioactives also beneficially affect platelet function, and with less side effects, albeit that effects are generally more subtle. Therefore, consumption of dietary bioactives could play a role in the prevention of atherothrombotic vascular disease. Here we review the efficacy of dietary treatment strategies, especially those involving certain dietary fatty acids and polyphenols, to modulate platelet function in healthy subjects or in patients with cardiovascular disease. Variation in study populations, small study sizes and lack of comparability between methods to assess platelet function currently limit robust evidence on the efficacy of dietary bioactives in healthy subjects or specific patient groups. Also, limited knowledge of the metabolism of dietary bioactives, and therefore of the bioavailability of bioactive ingredients, restricts our ability to identify the most effective dietary regimes to improve platelet function. Implementation of uniform point-of-care tests to assess platelet function, and enhanced knowledge of the efficacy by which specific dietary compounds and their metabolites affect platelet function, may enable the identification of functional anti-platelet ingredients that are eligible for a health claim, or combined treatment strategies, including both pharmacological anti-platelet treatment as well as dietary intervention, to tackle atherothrombotic vascular disease.

Abstract 54: Diminished Endothelial Fibrinolytic Function With Prehypertension

Prehypertension (systolic blood pressure: 120-139 mm Hg and/or diastolic blood pressure: 80-89 mm Hg) affects ~30% of the US adult population and is associated with increased atherothrombotic vascular disease risk. The underlying mechanisms responsible for this heightened risk are unclear. The capacity of the endothelium to release tissue-type plasminogen activator (t-PA), the primary activator of the fibrinolytic system, is an important endogenous defense mechanism against intravascular fibrin deposition and thrombosis. As part of an ongoing study, we are determining whether the capacity of the endothelium to release t-PA is impaired in adults with prehypertension. To date, 22 sedentary, non-obese middle-aged men have been studied: 12 normotensive (age: 53±2 yr; BP: 113/72±2/2 mm Hg) and 10 prehypertensive (age: 55±2 yr; BP: 133/85±2/1 mm Hg). All subjects were free of overt cardiometabolic disease. Net endothelial release of t-PA was determined, in vivo, in response to intrabrachial infusions of bradykinin (BK: 125-500 ng/min) and sodium nitroprusside (SNP: 2-8 μg/min). Endothelial t-PA release in response to each dose of BK was significantly lower (~50%) in the prehypertensive (from -1.7±0.7 to 34.1±5.7 ng/100 mL tissue/min) vs the normotensive (from 0.6±1.4 to 54.1±5.7 ng/100 mL tissue/min) adults. Total amount of t-PA released (area under the BK curve) was ~40% less (P&lt;0.05) in the prehypertensive compared with normotensive group (210±32 vs 336±45 ng/100 mL tissue). There was no effect of SNP on t-PA release in either group. In the overall study population, there was a significant inverse relation between both systolic (r=-0.44) and mean arterial (r=-0.42) blood pressure and total t-PA release. No other anthropometric, hemodynamic or metabolic variable was associated with t-PA release. These initial results indicate that the capacity of the endothelium to release t-PA is impaired in prehypertensive men. Diminished endothelial fibrinolytic capacity may contribute to the increased atherothrombotic risk with prehypertension.

Antithrombotic Therapy for Patients With Atrial Fibrillation and Atherothrombotic Vascular Disease

Antithrombotic Therapy for Patients With Atrial Fibrillation and Atherothrombotic Vascular Disease

Proposal of a new strategy for ambulatory blood pressure profile-based management of resistant hypertension in the era of renal denervation

In Asian populations, a high prevalence of stroke, high salt intake and high salt sensitivity, the effects of which are partly augmented by epidemic obesity, are associated with hypertension. These factors are closely associated with resistant hypertension, especially with the disrupted circadian rhythm of blood pressure (BP), that is, non-dipper and riser patterns. An ambulatory BP profile-based strategy combined with medication and devices (renal denervation and baroreceptor activation therapy) would help to achieve 'perfect 24-h BP control', consisting of strict reduction of the 24-h BP level, restoring disrupted circadian BP rhythms and reducing excess BP variability. Such BP control would protect high-risk patients with resistant hypertension against systemic hemodynamic atherothrombotic syndrome (which involves systemic atherothrombotic vascular diseases and target-organ damage, advanced by the composite risks of pulsatile hemodynamic stress from central pressure and blood flow and by thrombometabolic risk factors). Information technology-based home sleep BP pressure monitoring may be useful for assessing the risk during sleep in high-risk patients with resistant hypertension and sleep apnea syndrome.

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3(-/-);Ldlr(-/-) mice were no different from RIP3(+/+);Ldlr(-/-) mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe(-/-) background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3(-/-);Ldlr(-/-) and RIP3(+/+);Ldlr(-/-) mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3(-/-) mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL)-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.

Is prolactin involved in the evolution of atherothrombotic disease?

Cardiovascular diseases (CVDs) account for approximately 30% of all deaths globally. The most important cause of CVD is atherothrombosis, in other words, narrowing of the arteries as a result of the deposition of cholesterol and other lipoid substances within the arterial wall. Several endocrine disorders have been linked to this pathological state. Recent clinical and experimental studies have suggested that prolactin, a pleiotropic pituitary hormone, may potentially contribute to CVD, either through direct modulation of local cellular processes within atherosclerotic plaques/thrombi and/or through influencing conventional cardiovascular metabolic risk factors. However, the precise role of prolactin in the pathology of CVD remains largely unknown. Here, the authors speculate whether prolactin-lowering treatment may become a future therapeutic approach in patients with elevated prolactin levels and concomitantly presenting with coexisting vascular disease or a significantly elevated risk for premature atherothrombotic vascular disease. Awareness of these new developments may also change our clinical opinions about therapeutic strategies in patients with prolactinomas.