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Year : 2022  |  Volume : 35  |  Issue : 4  |  Page : 1630-1634

Effect of matrix metalloproteinase-9 on angiographic criteria of coronary ectasia

Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission10-Jul-2022
Date of Decision13-Sep-2022
Date of Acceptance24-Sep-2022
Date of Web Publication04-Mar-2023

Correspondence Address:
Remon S Adly
Faculty of Medicine, Menoufia University, Menoufia 32511
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mmj.mmj_233_22

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The aim of this study was to evaluate the correlation between serum levels of a specific matrix metalloproteinase, matrix metalloproteinase-9 (MMP-9), and the angiographic criteria of coronary artery ectasia (CAE).
Previously, CAE was thought to be a possible manifestation of atherosclerosis, and the relation between matrix metalloproteinase in particular MMP-9 and presence and severity of CAE was not clearly established by previous investigators.
Patients and methods
A retrospective study of 100 eligible patients with CAE was studied regarding their clinical presentation, angiographic criteria, and relation of the severity of CAE to serum level of MMP-9. We included assessment of major cardiovascular risk factors.
There were high serum levels of MMP-9 (>71 ug/dl) in 45% of patients with CAE, and there was a statistically significant relation (P = 0.035) of serum levels of MMP-9 with the number of ectatic vessels (100% for three-vessel disease vs. 43.38% for single-vessel ectasia). Moreover, we found a significant relation with the type of ectasia (83.33% for type 1 vs. 40% for type 2), with P = 0.015.
There is a considerable relationship between elevated levels of MMP-9 and CAE, as well as the relationship between levels of MMP-9 and severity of the CAE.

Keywords: atherogenesis, coronary angiography, coronary arteries, ectasia, extracellular, matrix metalloproteinase-9, matrix

How to cite this article:
Mousa WF, Elshafey WE, Adly RS. Effect of matrix metalloproteinase-9 on angiographic criteria of coronary ectasia. Menoufia Med J 2022;35:1630-4

How to cite this URL:
Mousa WF, Elshafey WE, Adly RS. Effect of matrix metalloproteinase-9 on angiographic criteria of coronary ectasia. Menoufia Med J [serial online] 2022 [cited 2023 Oct 3];35:1630-4. Available from: http://www.mmj.eg.net/text.asp?2022/35/4/1630/370989

  Introduction Top

The abnormal enlargement of one or more coronary segments is known as coronary artery ectasia (CAE). Ecstatic vessels have diameters that are at least 1.5 times larger than the surrounding, healthy vascular segment [1],[2]. Traditionally, CAE is divided into four categories [3]: type I is diffuse ectasia involving two or more vessels, type II is diffuse disease in one vessel and localized in another, type III is diffuse ectasia involving only one vessel, and type IV is localized segmental ectasia.

There is still much to learn about the etiopathogenesis of CAE. Matrix metalloproteinases (MMPs), proteolytic enzymes that are a component of a wide family of proteases known as a zinc-dependent endopeptidase, have been implicated in aberrant extracellular matrix (ECM) disintegration, among other theories. MMPs have been linked to a number of physiological and pathological processes, including tumor invasion, skin and lung illnesses, and according to some research, even the development of CAE [4],[5]. These enzymes were included also in fetal development, wound healing, and reproduction [6],[7].

Additionally, MMPs may contribute to the formation of aortic aneurysms by the proteolysis of ECM proteins and a reduction in the blood levels of tissue inhibitors of MMPs according to Eitan and Roguin [2].

Our study's objective was to study the correlation between serum levels of a specific metalloproteinase, MMP-9, and the angiographic criteria of CAE.

  Patients and method Top

In our retrospective study, we evaluated 965 coronary angiography procedures performed in the Cardiovascular Department of Menoufia Faculty of Medicine between March 2021 and April 2022. Informed consents were taken from all patients with approval of Ethics Committee of Menoufia University.

CAE was found in 100 patients, with a prevalence of ∼10.3%.

Exclusion criteria were prior coronary angioplasty, prior aortocoronary bypass surgery, and valvular heart disease.

Age; sex; the most prevalent risk factors for cardiovascular disease, such as hypertension, dyslipidemia, diabetes mellitus, and smoking; and the clinical justification for coronary angiography were all noted for each patient.

At a rate of 12.5 frames per second, digital angiographic pictures were captured using an angiography Philips Integris 2000 (philips: Harvey IL 60426 ,USA).

According to coronary angiography, we assessed the following:

  1. Which vessels were ectasia most likely to affect?
  2. The number of ectatic coronary arteries.
  3. The ectasia type (I, II, III, or IV).

A venous blood sample was taken from each patient a month or so after discharge to check their MMP-9 levels.

The samples were centrifuged for 10 min at 4°C, after which the serum was divided into aliquots and stored at −20°C. The kit Human MMP-9 (RayBioPantech: Norcross, GA 30092, Germany) was used to determine the level of metalloproteinases. We used a straight sandwich enzyme-linked immuno-sorbent assay kit.

Statistical analysis

Data were analyzed using STATA, version 14.2 (Stata Statistical Software: Release 14.2; StataCorp LP, College Station, Texas, USA). Quantitative data were represented as mean and SD. Data were analyzed using Student t test to compare means of two groups. Qualitative data were presented as number and percentage. Graphs were produced using Excel or STATA program.

  Results Top

The average age of the patients in our research who had CAE was 52.24 years, and 65% of them were men [Table 1].
Table 1: Demographic data and risk factors of the studied population

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We assessed the conventional cardiovascular risk factors and discovered their overlap. In instance, the majority of patients (53% of them) had dyslipidemia and arterial hypertension (52%). In contrast, diabetes mellitus was underrepresented in our population (43%). Overall, 34% of the patients were smokers [Table 1].

Angina (chronic coronary syndrome), which affected 64% of patients, was the most common reason for coronary angiography, followed by acute coronary syndrome (36%) [Table 2].
Table 2: Clinical presentation, angiographic findings, and matrix metalloproteinase-9 level of studied population

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Of all patients, 83% had one CAE on angiography, 14% had two-vessel ectasia, and only 3% had three-vessel ectasia. The RCA was the most common site of coronary ectasia, with a percentage of 55%, followed by left anterior descending (LAD) (48%) and left circumflex (LCX) (17%). Additionally, our patients varied in terms of the type of ectasia they had according to Markis classification [3], with type 4 being the most prevalent (70%), followed by types 3, 2, and 1, with representations of 13, 11, and 6%, respectively, as shown in [Table 2].

In our study, we discovered that 45% of individuals with CAE had high blood levels of MMP-9 (>71 ug/dl), with an average of 176 ug/dl [Table 2].

Additionally, we discovered that the high serum level of MMP-9 was statistically significant (P = 0.035) in direct proportion to the number of coronary arteries with ectasia (100% for three-vessel disease vs. 43.38% for single-vessel ectasia), as shown in [Figure 1] and [Table 3].
Figure 1: Relation between and number of ectatic vessels. MMP-9, matrix metalloproteinase-9

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Table 3: Relation between matrix metalloproteinase-9 level of studied population and number of ectatic vessels

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Moreover, we found a significant increase in serum MMP-9 levels (P = 0.015) in relation to the type of ectatic vessels, with type 1 accounting for 83.33% of them and type 4 for 40% [Figure 2] and [Table 4].
Figure 2: Relation between MMP-9 and type of ectasia. MMP-9, matrix metalloproteinase-9

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Table 4: Relation between matrix metalloproteinase-9 level and type of ectasia

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  Discussion Top

In accordance with our analysis, Eitan and Roguin [2] and Dahhan [8] reported that the clinical relevance of CAE, a relatively prevalent disease in the population, has only lately been realized, and epidemiological statistics derived from other studies allow us to estimate that between 1.4 and 7.4% of patients subjected to coronary angiography would have CAE, with a greater prevalence in males, as shown by Giannoglou et al. [9] and Pinar et al. [10].

Patients with CAE had significant prevalence of the major cardiovascular risk factors, such as high blood pressure, which was found in 85.1% of patients. According to the data in the literature, diabetes mellitus and coronary aneurysms have an inverse relationship. This is because, despite being a major risk factor for atherosclerosis, diabetes mellitus is underrepresented in the population of patients with coronary aneurysms, likely because it favors contraction-type remodeling over expansion-type remodeling. This agrees with studies shown by Androulakis et al. [11] and Yetkin et al. [12].

The right coronary artery, anterior descending artery, and circumflex artery in order were the most affected by the CAE. The common trunk of the left coronary artery is much less targeted in percentage terms. This is consistent with Mavrogeni [13] and Lamblin et al. [14].

The clinical manifestation of CAE might vary. It is frequently discovered incidentally during coronary angiography, after experiencing angina pectoris or acute coronary syndrome, or both. In fact, myocardial infarction and angina pectoris are significantly more common in individuals with CAE according to Akyürek et al. [15], and changes in coronary flow are likely the pathophysiological cause of the start of ischemic events as shown by Baman et al. [16].

Brunetti et al. [17] and Kuramochi et al. [18] stated that dilated segment's sluggish or even stagnant flow might activate platelets, trigger the coagulation cascade, and encourage thrombus formation.

In our present study, chronic coronary syndrome (64%) and acute coronary syndrome were the two most common reasons for coronary angiography. (36%), and they are the most common forms of clinical presentations of CAE.

In a study done by Dogan et al. [19] and Dendramis et al. [20], the ECM and the enzymes involved in its remodeling appear to have a pathogenetic role in the onset of CAE. They were shown to play a significant role in this, as they control aberrant ECM breakdown in response to biochemical and local hemodynamic shocks, enabling excessive expansive remodeling of the vascular wall and the onset of CAE.

According to the current literature, we discovered high levels of MMP-9 in 45% of our patients, with a statistically significant increase in levels directly proportional to the number of ectatic vessels and a highly significant increased levels in direct proportion to the type of ectasia.

As CAE and coronary artery disease (CAD) frequently coexist and share similar histological features, there has been speculation, especially in the past, that the CAE may be a feature of atherosclerosis. However, current research suggests that the CAE may be distinct from coronary atherosclerosis, despite the fact that it causes similar symptoms and damaging insults to myocardial tissue but has an inverse relationship with age and diabetes mellitus. Additionally, the patients with CAE have higher levels of MMPs than CAD and a greater involvement of the right coronary artery in the CAE than in CAD [21].

  Conclusions Top

It appears that some ECM degrading enzymes, such as MMPs, play a significant role in the development of CAE, despite the fact that the pathogenetic processes underlying the disease remain largely understood. We discovered a potential link between particularly high MMP-9 levels and CAE as well as a link between MMP-9 levels and the severity of the CAE.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Liu R, Chen L, Wu W, Chen H, Zhang S. Extracellular matrix turnover in coronary artery ectasia patients. Heart Vessels 2016; 31:351–359.  Back to cited text no. 1
Eitan A, Roguin A. Coronary artery ectasia: new insights into pathophysiology, diagnosis and treatment. Coron Artery Dis 2016; 27:420–8.  Back to cited text no. 2
Markis JE, Joffe CD, Cohn PF, Feen DJ, Herman MV, Gorlin R. Clinical significance of coronary arterial ectasia. Am J Cardiol 1976; 37:217–222.  Back to cited text no. 3
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Kandhwal M, Behl T, Singh S, Sharma N, Arora S, Bhatia S. Roles of matrix metalloproteinases in cutaneous wound Heal ing. In: Alexandrescu V. A, editor. Wound healing – new insights into ancient challenges. London: IntechOpen; 2016. 10.5772/64611.  Back to cited text no. 6
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Dahhan A. Coronary artery ectasia in atherosclerotic coronary artery disease, inflammatory disorders, and sickle cell disease. Cardiovasc Ther 2015; 33:79–88.  Back to cited text no. 8
Giannoglou GD, Antoniadis AP, Chatzizisis YS, Damvopoulou E, Parcharidis GE, Louridas GE. Prevalence of ectasia in human coronary arteries in patients in northern Greece referred for coronary angiography. Am J Cardiol 2006; 98:314–8.  Back to cited text no. 9
Pinar Bermúdez E, López Palop R, Lozano Martínez-Luengas I, Cortés Sánchez R, Carrillo Sáez P, Rodríguez Carreras R, et al. Coronary ectasia: prevalence, clinical and angiographic characteristics. Rev Esp Cardiol 2003; 56:473–479.  Back to cited text no. 10
Androulakis AE, Andrikopoulos GK, Kartalis AN, Stougiannos PN, Katsaros AA, Syrogiannidis DN, et al. Relation of coronary artery ectasia to diabetes mellitus. Am J Cardiol 2004; 93:1165–1167.  Back to cited text no. 11
Yetkin E, Waltenberger J. Novel insight into an old controversy: is coronary artery ectasia a variant of coronary atherosclerosis?. Clin Res Cardiol 2007; 96:331–339.  Back to cited text no. 12
Mavrogeni S. Coronary artery ectasia: from diagnosis to treatment. Hellenic J Cardiol 2010; 51:158–163.  Back to cited text no. 13
Lamblin N, Bauters C, Hermant X, Lablanche JM, Helbecque N, Amouyel P. Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurismal coronary artery disease. J Am Coll Cardiol 2002; 40:43–48.  Back to cited text no. 14
Akyürek O, Berkalp B, Sayin T, Kumbasar D, Kervancioğlu C, Oral D. Altered coronary flow properties in diffuse coronary artery ectasia. Am Heart J 2003; 145:66–72.  Back to cited text no. 15
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Brunetti ND, Salvemini G, Cuculo A, Ruggiero A, De Gennaro L, Gaglione A, Di Biase M. Coronary artery ectasia is related to coronary slow flow and inflammatory activation. Atherosclerosis 2014; 233:636–640.  Back to cited text no. 17
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Dendramis G, Paleologo C, Lo Presti A, Piraino D, Lo Greco V, Grassedonio E, et al. Coronary artery ectasia: etiopathogenesis, diagnosis and treatment. G ItalCardiol (Rome) 2014; 15:161–9.  Back to cited text no. 20
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4]


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