Vascular Pathobiology

S. Xu , ... A.I. Gotlieb , in Cardiovascular Pathology (Fourth Edition), 2022

Vessel Wall Remodeling

The avenue wall adapts to the presence of an atherosclerotic plaque. Equally the plaque encroaches on the vessel lumen, the wall of the vessel undergoes remodeling to maintain normal lumen size. Hemodynamic shear stress is an important regulator of this process. Information technology is likely that cell proliferation, apoptosis, and both matrix synthesis and degradation are important modulating factors in the artery wall. It is also probable that the plaque itself undergoes remodeling and that apoptosis may exist an important procedure since factors associated with its regulation are found in plaques. Once a plaque encroaches on nearly 45% of the lumen, compensatory remodeling cannot maintain lumen size and information technology narrows. Alterations in the syntheses or effectiveness of vasoactive substances may interfere with the adaptive procedure—for example, as might occur with decreased synthesis of nitric oxide (NO) by ECs or reduced responsiveness of SMCs to NO which would attenuate vasodilation in response to increased blood flow and forestall adaptive outward remodeling.

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Coronary Artery Dissection

In Diagnostic Pathology: Cardiovascular (Second Edition), 2022

Cardinal FACTS

Terminology

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Coronary artery wall injury resulting from intimal rupture with subsequent disruption of vessel wall, which leads to double lumen formation, obliteration of lumen, and secondary myocardial ischemia

Etiology/Pathogenesis

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Spontaneous

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Pregnancy/post partum

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Cocaine corruption

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Iatrogenic

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Mail coronary catheterization

Clinical Issues

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Young female patients without coronary disease have 3x higher occurrence than male patients

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Clinical presentation depends on extent of dissection flap and degree of luminal occlusion and varies from asymptomatic to sudden death

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Site involved

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Most mutual involvement of left anterior descending branch (in females)

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Right coronary (in males) and circumflex branch

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Left main coronary rarely involved

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Conservative and surgical approaches vary based on localization, accessibility, and extent of autopsy too every bit patient stability and severity of ischemia

Microscopic

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Intimal tear may not exist demonstrated

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Unremarkable media

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Adventitial eosinophils

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Angiomatous changes

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Myocardial ischemia may be nowadays

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Vasculitis and cystic media necrosis are infrequent

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Atherosclerosis and Coronary Artery Illness

M. Zaromitidou , ... D. Tousoulis , in Cardiovascular Diseases, 2022

Normal Artery Structures

The normal artery wall comprises three layers: the tunica intima, the tunica media, and the tunica adventitia.

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The tunica intima consists of the endothelium, connective tissue (collagen, laminin, fibronectin, and other extracellular matrix molecules), and a basal layer of elastic tissue called internal elastic lamina that separates the tunica intima from tunica media. Endothelium is a sparse monolayer of cells that serves every bit the contact surface with blood. Due to its strategic location, the endothelium has emerged every bit the chief regulator of vascular homeostasis with its structural and functional properties contradistinct in response to local and systemic stimuli [v].

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The tunica media is characterized by the presence of concentric layers of vascular smooth muscle cells (VSMCs) and elastin-rich extracellular matrix. It is the final recipient of signals regulating the vascular tone and is separated from adventitia past the external rubberband lamina.

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The tunica adventitia is the outer layer of the vascular wall, and it consists of fibroblasts, collagen, mast cells, nervus endings, and vasa vasorum. It was non until recently that important functions of the adventitia were identified. More specifically, adventitia seems to participate in the cell trafficking through the arterial wall and the signaling between vascular endothelial cells, smooth muscle cells, and the local tissue environment. In add-on, this layer is involved in the repair mechanism following vessel injury, in the regulation of the dynamic lumen size (via medial smooth muscle tone), and in the inwards or outward wall-remodeling response [six].

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The Arterial System in Human Hypertension

Daniel A. Duprez , Jay Northward. Cohn , in Comprehensive Hypertension, 2007

CONCLUSIONS

Recognition that the artery wall is an important target of the disease we aim to care for has stressed the need for monitoring techniques to identify effective treatments in trials and to track individual patients for the natural history of their illness and the efficacy of interventions. Although data using existing technologies are still limited in scope and follow-up, pulse wave analysis is peculiarly attractive because of its simplicity and credible sensitivity. Pulse wave velocity also is relatively unproblematic, but its confinement to the aorta and large conduit arteries limits its application to identifying structural changes in the big arteries. Reproducibility and liberty from extraneous influences are critical to the application of methods for monitoring. Claret force per unit area measurement itself is neither reliably reproducible nor free from inapplicable influences. Nonetheless, BP has served in population studies every bit a guide to cardiovascular risk. Its utilize in individuals, however, usually is buttressed past repeated measurements, either in the function or at dwelling house, by exclusion of outlying measurements, and past sensation of environmental atmospheric condition at the time of measurement. Cess of the mechanical properties of the small and large arteries has the potential to be far more sensitive and specific for detecting CV disease and the response to drug therapy than the BP alone. 44

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Phase of Reproductive Life, Atherosclerosis Progression and Estrogen Furnishings on Coronary Artery Atherosclerosis

THOMAS B. CLARKSON , JAY R. KAPLAN , in Treatment of the Postmenopausal Woman (Tertiary Edition), 2007

1 DIMINISHED ER EXPRESSION OR Activity

Availability of ERs in the artery wall is considered an important factor in how estrogens can modulate development of atherosclerosis. Losordo and colleagues ( 105) demonstrated loss of detectable ERs in atherosclerotic arteries. ER'south were detectable in 71% of normal arteries simply were found in only 32% of arteries with atherosclerosis (p = 0.01). Post and colleagues (106) reported a greater degree of ER-α methylation in coronary atherectomy samples (ten%) compared with macroscopically normal human aorta (4%, p < 0.01 versus atherectomy). Reduced expression or action of the ERs in atherosclerotic lesions would contribute importantly to the lack of protection afforded by ET in patients with advanced atherosclerosis.

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Mycotic Aneurysm

In Diagnostic Pathology: Cardiovascular (Second Edition), 2022

Key FACTS

Terminology

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Aneurysm that results from or is secondarily infected by organisms (commonly bacteria) arising from distant site of infection

Etiology/Pathogenesis

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Principal: Infection of artery wall with secondary aneurysm development (uncommon)

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Secondary: Infection occurs in preexisting atherosclerotic aneurysm; ordinarily arises from distant site (e.g., heart valve endocarditis, bacteremia)

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Routes of wall infection include implantation on intimal surface, embolization of bacteria into vasa vasorum, directly extension of infection from face-to-face extravascular site, traumatic inoculation, and lymphatic spread

Clinical Issues

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Incidence: Unknown but estimated to exist 0.65-2.00% of all aortic aneurysms

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Symptoms: Fever, localized pain, sepsis, pulsatile mass

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Germination of aneurysm may evolve chop-chop, over course of days, subsequently initiation of aortitis

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Rupture is frequent (75%) without surgical and antibiotic treatment

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Mortality rate estimated at 67% without treatment

Imaging

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Rapidly growing saccular aneurysm arising eccentrically from aortic wall

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Tin can involve any role of aorta wall or other vessels

Macroscopic

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Saccular outpouchings are most common type

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Thin wall with periaortic inflammatory changes

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Marked edema of adventitia

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Calcification is uncommon

Microscopic

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Transmural acute inflammation with microabscesses, chronic inflammatory infiltrate, nonnecrotizing granulomatous inflammation; pseudoaneurysm, adventitia with chronic inflammation and dense fibrosis

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Endothelial Prison cell and Smooth Muscle Cell Biology in Vascular Disease

Richard D. Kenagy , Alexander W. Clowes , in Surgical Research, 2001

a. No-Flow Conditions

Several variations of culturing whole wall avenue have been used. Rectangular pieces of rat (185, 186), rabbit (187), squealer (188, 189), and human aorta (190, 191) and saphenous vein (192) have been placed in culture dishes with standard culture medium with or without serum. Serum causes necrosis to occur (187, 188), whereas in serum-costless conditions cell morphology remains normal. A significant intima is developed in culture. Nicosia and colleagues (193) take suspended rat aortic rings in collagen gels and then placed these in standard civilization dishes every bit a model of angiogenesis. Because the density of cells in the tissue is high, the medium is more often than not changed frequently (187). For case, a 1-cm2 segment of rabbit aorta requires x ml of medium, changed every 2 days (J. Fingerle, personal communication, 1999).

Adenoviral vectors have been used to overexpress genes of interest—for example, TIMP-one (194)—in the saphenous vein model. This is of particular interest because of the possibility of treating vessels before use in bypass grafting procedures. An extension of the elastase-induced aneurysm model in vivo has been made to organ culture by incubating porcine aorta in elastase in vitro. Post-obit this treatment in that location is a progressive loss of elastin (195).

Ane aspect of these organ cultures, particularly vein organ cultures, that requires attending is determining the origin of neointimal cells. Cut edges could allow adventitial cells to drift around and onto the intimal surface. This issue is not entirely settled. Adventitial fibroblasts have been shown to populate the intima of human saphenous veins in vitro (196) and porcine saphenous veins in vivo (197), so each investigator should put some effort into understanding the origin of intimal cells if this is pertinent to their goals.

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Disorders of Lipid Metabolism

Dirt F. Semenkovich , ... Ira J. Goldberg , in Williams Textbook of Endocrinology (Thirteenth Edition), 2022

Unstable Plaque and Regression

The atherogenic procedure occurs within the artery wall. Initially, information technology was thought that the lumen was progressively narrowed by the aggregating of macrophages, the proliferation of smooth muscle cells, and the degradation of cholesterol. In fact, the truly dangerous lesion (the culprit lesion) may non cause marked luminal narrowing. 132 Equally atherosclerosis progresses, there is a compensatory expansion of the lumen that maintains an nearly constant lumen size. As the lesion develops inside the intima, the complication of rupture of the overlying intima or endothelial erosion leads to exposure of the lesional contents to platelets, initiating thrombosis. It is the acute thrombosis that is responsible for infarctions in virtually patients. Rupture or erosion occurs where the fibrous cap covering the underlying thrombogenic lipid is thin.

The surfaces of complicated lesions can get thrombogenic as endothelial cells are lost or the fibrous cap ruptures and the subendothelial space is exposed. Platelets can adhere to this exposed surface, promoting thrombus formation. In these unstable plaques, blood actually dissects into the avenue wall, leading to the formation of a large thrombus. Calcification is as well a feature of belatedly lesions. Advanced lesions can weaken the elasticity and integrity of the artery wall, potentially creating an aneurysm of the vessel. Equally clinical trial data accept shown, removal or reduction of the atherogenic stimulus can event in plaque regression and stabilization, leaving a remnant devoid of lipid that resembles a wound scar and is less likely to serve every bit a nidus for thrombus formation.

Atherosclerosis usually develops in the setting of hypercholesterolemia. Observations first made in animals and now confirmed in humans betoken that this process can be reversed if plasma cholesterol reduction is intensive. 133

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Volume 2

Eric A. Osborn , ... Farouc A. Jaffer , in Molecular Imaging (Second Edition), 2022

Leukocyte Trafficking Imaging, Plaque Progression, and Recurrent MI

Recruitment of circulating monocytes to the artery wall is a crucial stride in the formation of fat streaks also as atheroma evolution [ 18,259]. In vivo study using molecular imaging tin can interrogate these dynamic biological processes.

After an acute coronary syndrome, patients remain at heightened cardiovascular hazard. The cardiosplenic axis, a link between the spleen, bone marrow, and atherosclerotic plaques, can replenish leukocytes that enter plaques, produce proinflammatory cytokines locally, and promote plaque progression. In a pilot study, FDG uptake in the spleen of 22 patients following an astute coronary syndrome exceeded that in control subjects (SUV: 2.6   ±   0.six vs. two.1   ±   0.3, P  =   .03) [260]. A split up arm of this trial including 464 patients without known cardiovascular disease revealed that those with increased FDG uptake in the spleen suffered more frequent cardiac events of 4 years of follow-up (Fig. 62.6), even when bookkeeping for other cardiovascular risk factors (Hour 3.3, 95% confidence interval 1.five–7.3, P  =   .003). PET reporters on in vivo cellular proliferation in plaques and hematopoietic tissue have also been developed, as shown for 18F-fluorothymidine (18F-FLT), an agent extensively characterized in preclinical mice and rabbits that likewise localizes within bone marrow of individuals following acute myocardial infarction and within inflamed human atheroma [261]. Preventative strategies that can interrupt the cardiosplenic centrality may accept clinical utility to break the wheel of proinflammatory leukocyte migration [iii].

Figure 62.6. FDG-PET/CT provides molecular imaging insights into the systems biology of atherosclerosis, extramedullary and medullary reservoirs of inflammatory cells, and clinical events.

PET/CT images of the aorta, os marrow, and spleen afterward FDG administration in a patient with an acute coronary syndrome versus a good for you control demonstrates significant point uptake in the arterial wall of the aorta, bone marrow, and spleen compared to the command. Os marrow and splenic FDG uptake were both significantly associated with increased risk of future cardiovascular events.

 Emami H, Singh P, MacNabb M, Vucic Eastward, Lavender Z, Rudd JH, Fayad ZA, Lehrer-Graiwer J, Korsgren Grand, Figueroa AL, Fredrickson J, Rubin B, Hoffmann U, Truong QA, Min JK, Baruch A, Nasir Yard, Nahrendorf M, Tawakol A. Splenic metabolic activity predicts risk of future cardiovascular events: sit-in of a cardiosplenic axis in humans. JACC Cardiovasc Imaging 2022;8:121–130.

Monocyte recruitment to plaques has as well been explored using SPECT imaging. 111Indium oxyquinoline (111In-oxine), incubated ex vivo with purified claret monocytes has been utilized for SPECT tracking in vivo [262,263]. Afterwards early transient stops in the eye and lungs, 111In-oxine monocytes localized in the spleen at 48–72   h before eventually homing to atherosclerotic plaques past twenty-four hour period five afterwards adoptive transfer. In a split written report, 99mTc-labeled autologous peripheral blood mononuclear cells (99mTc-PBMC) were employed to track leukocyte homing to atherosclerotic plaques in vivo in 10 patients [264]. Six hours later on administration, 99mTc-PBMC tended to accumulate to a greater extent in more diseased arteries (TBR: 2.1 vs. 1.5, P  =   .04). 99mTc-PBMC signal also correlated well with baseline FDG-PET action (r   =   0.88, P  <   .001), suggesting that more inflamed plaques invite more leukocyte influx.

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Experimental models for identifying target events in vascular injury

Thais Girão-Silva , ... Silvia Lacchini , in Endothelial Signaling in Vascular Dysfunction and Disease, 2022

16.5 Vein graft accommodation to new hemodynamic status

Equally is well known, veins and arteries walls are formed by 3 layers: (1) Intima—monolayer of endothelial cells under a basal lamina, known as endothelium; (2) Media—a muscular layer with SMCs and extracellular matrix; (3) Adventitia—rich in fibroblast, matrix, and capillaries to supply the vessel (vasa vasorum) [42]. While arteries are constantly exposed to high blood pressure and flow, venous system is a pulseless, depression pressure level, and low menstruum system [35,43]. Thus, coronary arteries have a greater muscular layer and robust rubberband laminas (internal and external) to support and accommodate arterial mechanical stress [36] while saphenous veins have thinner media layer and are less elastic, which increases their capacitance. Likewise, veins have valves to provide unidirectional flow [42].

A human vein environment has depression pressure (five–8   mmHg) and shear stress estimated around 0.two   dynes/cmtwo [44,45]. Thus, post CABG, the saphenous vein graft is suddenly submitted to an arterial hemodynamic status with great increase in pulsatile pressure (120/80   mmHg), college cyclic stretch (10%–15%) and shear stress (15–20   dynes) [41,46]. Acute changes in mechanical condition are compensated by vascular tonus control. Long-term mechanical load induces a permanent alteration with modification in the vessel wall structure named every bit vascular remodeling [47]. The increase in intraluminal force per unit area induces wall thickness to adjust tangential stress and normalize vessel tension [48]. This is an adaptive process, likewise termed vein arterialization, which involves endothelium denudation, invasion of inflammatory cells, increase number of SMC like cells for e.g., cells positive to smoothen muscle actin (αSMA), cell migration and extracellular matrix production (collagen and elastin) that creates a medial thickening and neointima layer [37,38,49].

Vein graft apoplexy in some patients occurs due to an imbalance in this remodeling, which culminates in exacerbated neointima increase. Many questions remain unclear such as: why some grafts take better adaptation than others, the molecular mechanisms responsible for tissue restructuring or what interventions or strategies can be used to attune the pathway to avoid excessive remodeling.

To answer those questions, experimental models are all-time suited as they enable the study of molecular pathways associated with a single stimulus. Thus,changes in shear stress and stretching that occur simultaneously in a vascular graft, can exist studied individually using in vitro and in situ experimental devices. Organ culture (ex vivo) systems accept the reward of closely mimicking human samples in a more controlled status. In improver, animal models (in vivo) accept largely been used to validated data obtained in in vitro and ex vivo models and besides to test therapeutic strategies.

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