What Are the Different Types of Recognition Plaques?

Vulnerable Plaque refers to those plaques that are unstable and prone to thrombosis, mainly including ruptured plaques, erosive plaques, and partially calcified nodular lesions.

Vulnerable plaque

Vulnerable Plaque refers to those plaques that are unstable and prone to thrombosis, mainly including ruptured plaques, erosive plaques, and partially calcified nodular lesions.

Vulnerable plaque definition

A large number of studies have shown that about 70% to 80% of arteriosclerotic thrombosis is caused by the rupture of mild and moderately narrowed arterial plaques and secondary thrombosis. However, plaque rupture is not the only content of vulnerable plaques. Those atheromatous lesions that are prone to thrombosis and may quickly progress to criminal plaques belong to the category of vulnerable plaques. Naghavi et al. Gave the histological definition and criteria of vulnerable plaques. The main criteria include active inflammation, thin fibrous caps and large lipid cores, exfoliation of endothelial cells with surface platelet aggregation, plaque fissures or lesions, and severe stenosis. Secondary criteria included surface calcified plaques, yellow shiny plaques, intraplaque hemorrhage, and positive remodeling. The factors that lead to plaque instability and vulnerability are systemic and may affect the arterial system widely. The focus of future treatment should not only be on vulnerable plaques, but also on "fragile blood" (referred to as hypercoagulable blood) , Vulnerable to thrombosis), vulnerable patients; therefore, comprehensive assessment based on vulnerable plaque and vulnerable blood is more clinically meaningful.

Basic characteristics of vulnerable plaques

Vulnerable plaque plaque rupture

Plaque rupture refers to the fissures that extend to the lipid core, often accompanied by a loss of the fibrous cap rather than just the loss of the endothelium, and often non-occlusive thrombus composed of platelets and fibrin. Compared with intact plaques, ruptured plaques are characterized by a cholesterol-rich necrotic core and a thin fibrous cap. There are fewer smooth muscle cells in the fibrous cap and there are a large number of foamy macrophages, T lymphocytes, and mast cells. Aggregation, with plaque most prominent around the shoulder. When the proportion of atheroma in the plaque is greater than 30% -40%, the possibility of plaque rupture significantly increases. In recent years, thin fiber caps have gradually attracted people's attention. Because the average thickness of the plaque fiber cap is (23 ± 19) & micro; m, 95% of which are less than 64 & micro; m, so the fiber cap thickness <65 & micro; m is considered as the main feature of the vulnerable plaque one. Plaque rupture tends to occur at the edge or peri-shoulder area of the plaque because these areas have thin fiber caps, are prone to necrosis, or are infiltrated by a large number of macrophages. Excessive extracellular lipid pools increase the fiber cap Of tension. Clinically, plaque rupture is the main cause of secondary thrombosis.

Fragile plaque

Approximately 25% -50% of the thrombus formations have no plaque rupture, but erosion of the endothelium can be seen. The inner membrane of the thrombus formation contains a large number of smooth muscle cells and glycoprotein matrices, and the inflammatory response is lighter, which is eroded plaque. Once this plaque appears, it is often diffuse, with extracellular lipid pools deep inside the intima, but necrosis is rare. Eroded plaques may be the result of repeated local spasms of the coronary arteries.

Pathophysiology of vulnerable plaque

Vulnerable plaque cells, inflammatory mechanisms and plaque vulnerability

The stability of the plaque is determined by a variety of factors. It is negatively related to the size of extracellular lipid pools and inflammatory cells, and positively related to the thickness of the fibrous cap. Therefore, the increase in the lipid pool, the increase in the number of inflammatory cells, and the thinning of the fiber cap lead to the vulnerability or instability of the plaque. Intraplaque inflammation is the key factor that causes plaque instability. Plaque rupture and plaque erosion almost always coexist with inflammation. In clinical instability, inflammation in plaque is always up-regulated [6]. The incidence and severity of superficial plaque inflammation are closely related to plaque rupture, which confirms the important role of plaque fibrous caps rather than deep plaque inflammation in plaque rupture. Inflammatory cells are recruited into plaques mainly through adhesion molecules and chemokines and activated by oxidized lipids, cytokines and the like. Factors involved in the recruitment and activation of inflammatory cells include increased angiotensin II activity, elevated arterial blood pressure, diabetes, infection, and immune activation. In addition, the increase in adventitial neovascularization also provides a pathway for inflammatory cells to enter the plaque fibrous cap. The study also found that the number of activated mast cells in the plaque erosion or destruction area is greater than that in the normal endometrial area, and after activation of mast cells, various mediators are released to promote the formation of foam cells, which directly or indirectly participate in the degradation of the extracellular matrix. Macrophages can also degrade the extracellular matrix through phagocytosis or release plasminogen activators, weakening the fiber cap.

Vulnerable Plaque Matrix Metalloproteinases and Plaque Vulnerability

The main component of the plaque fiber cap is the extracellular matrix, including collagen fibers and elastin, which are mainly synthesized and secreted by vascular smooth muscle cells, and their synthesis and degradation are also regulated by a variety of factors. Vascular smooth muscle cells have reduced extracellular matrix synthesis and / or proteolytic enzyme degradation of extracellular matrix, which are the main causes of plaque rupture. In one aspect, extracellular matrix synthesis is reduced. In unstable plaques, gamma interferon secreted by activated T lymphocytes can almost completely inhibit collagen fiber synthesis and affect the maintenance and repair of collagen tissue. Apoptosis plays an important role in the vulnerability of plaques. The enhancement of pro-apoptotic factors and / or the weakening of anti-apoptotic factors all lead to the apoptosis of endothelial cells and smooth muscle cells. In this way, the decrease in the number and function of smooth muscle cells has led to reduced synthesis and secretion of extracellular matrix, and impaired collagen repair of the fibrous cap. On the other hand, degradation of the extracellular matrix is increased. Macrophages and smooth muscle cell-derived foam cells can secrete proteases, mainly a group of zinc-containing matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1), which can first destroy the structure of collagen; gelatinase A and B (MMP-2 and MMP-9) can continue to break down collagen fragments; matrix degrading enzymes (MMP-3 and MMP-7) can break down the matrix, activate other MMPs zymogens to become active enzymes, and degrade elastin, Also decomposes polysaccharide core protein, the main component of extracellular matrix; human metalloproteinase (MMP-12), can activate all MMPs, not only decompose elastin, but also degrade all extracellular matrix such as type IV collagen, fibronectin, laminin, etc. ingredient.

The level of collagen molecules in the fibrous cap depends mainly on its balance of synthesis and disruption, which is regulated by cytokines through smooth muscle cells. There are complex regulation of MMPs in vivo, mainly including transcription level regulation, zymogen activation and MMPs inhibitors. Normally, MMP-1, MMP-2 and tissue metalloproteinase inhibitors expressed in vascular smooth muscle cells are in a state of equilibrium. However, under the action of inflammatory factors such as interleukin-1 and tumor necrosis factor-, the final The net effect is that the degradation of the extracellular matrix occupies a clear advantage, the strength of the fiber cap weakens, and the plaque becomes vulnerable.

Vulnerable plaque vascular endothelial cell dysfunction and plaque vulnerability

Vascular endothelial cells play a key role in the stabilization of blood vessels themselves. Endothelial dysfunction has long been seen in patients with diabetes, hypertension, smoking, dyslipidemia, and elevated plasma cysteine, although at this time the patient may not have obvious symptoms of atherosclerosis and ischemia. Endothelial cell dysfunction affects vascular tone, lipid metabolism, and coagulation mechanisms. Inflammatory cells activate and synthesize and secrete various hydrolytic enzymes, cytokines, and growth factors, leading to cell proliferation and eventually cell necrosis and the formation of unstable and complex plaques. . Vasodilators are relatively reduced, vasoconstrictors are relatively up-regulated, activated leukocytes easily enter the subvascular endothelium space, induce platelet aggregation, and increase the permeability of lipoproteins and plasma components. Hypercholesterolemia and other risk factors can facilitate this process. A large number of animal experiments and clinical intervention studies have confirmed that statins improve vascular endothelial cell function and stabilize plaque.

Vulnerable Plaque Lipid Metabolism and Plaque Vulnerability

Hypercholesterolemia can cause vascular endothelial cell dysfunction, and even without plaque rupture, hypercholesterolemia increases the risk of coronary thrombosis. More meaningfully, oxidatively modified low-density lipoprotein is a highly inflammatory and cytotoxic substance, which can induce macrophages, platelets, etc. to release a variety of growth factors and interleukins, leading to the proliferation and thickening of vascular smooth muscle cells And platelet aggregation and thrombosis, which adversely affects the coagulation and anticoagulation system. Calabri and other studies have shown that, regardless of the level of low density lipoprotein, the level of soluble cell adhesion factor in patients with low density lipoprotein is significantly lower than that of patients with normal density lipoprotein. In addition to the role of HDL in reversing cholesterol transport, studies by Spieker et al. Have shown for the first time that increasing HDL levels in the body can increase nitric oxide biological activity and improve endothelial function.

Peroxisome proliferator receptor (PPAR) is a ligand-activated nuclear transcription factor that regulates the function of a variety of inflammatory cells by regulating the expression of target genes. The gamma subgroup plays a central role in adipogenesis and lipid metabolism, activating PPAR- can inhibit the expression of a variety of pro-inflammatory factors, adhesion molecules and reduce the production of MMPs related to plaque progression. Studies show that PPAR- activators reduce the concentration of plasminogen activator inhibitor factor-1 and fibrinogen, increase fibrinolytic activity, and thus reduce thrombosis; more importantly, PPAR- activators promote the reverse of cholesterol at the gene level Transit [18].

Vulnerable plaque thrombosis and plaque vulnerability

Detection of vulnerable plaques

The timely identification and intervention of vulnerable plaque patients is of great significance for the prevention of ACS, which is also a research hotspot in recent years. Although coronary angiography is considered as a standard method for evaluating the anatomy of coronary arteries, it cannot show the specific changes of plaques, and there are unavoidable defects in identifying vulnerable plaques. In this way, new non-traumatic or traumatic detection methods based on catheter technology came into being. Each detection method has its own advantages and disadvantages, and the recognition performance for vulnerable plaque characteristics is also different. High-resolution intravascular ultrasound, optical coherence tomography, and vascular core magnetic resonance can detect lipid core size and fiber cap thickness. Angioscopy can detect vulnerable plaques by identifying the plaque surface features and color changes. The cholesterol crystals under the thin fiber cap have a specific energy absorption effect or Raman shift, which is the principle of spectroscopic spectroscopy or Raman spectroscopy. The surface of the vulnerable plaque has temperature heterogeneity. The infrared or other technology can be used to locate the thermal or metabolic activity to identify the highly vulnerable plaque. Different detection methods have different characteristics and can complement each other. For example, optical coherence tomography has high resolution but poor penetration, and intravascular ultrasound has good penetration and low resolution.

At present, a large number of studies have measured the MMPs and cytokines in circulating blood or even coronary circulation blood that can best reflect the pathophysiology of vulnerable plaques as possible alternative endpoints for predicting plaque vulnerability, but the conclusions require large-scale clinical validation. . Using high-resolution imaging technology to understand the local pathological basis, combined with the use of systemic markers to identify and judge plaque vulnerability may have greater clinical significance.

In short, the redefinition of vulnerable plaques and a deep understanding of its pathophysiology are helpful to the effective prevention and treatment of ACS. More important for the detection of vulnerable plaques is the flexible combination of multiple methods in order to screen out high-risk patients with high-risk plaques.