Fibrous-cap degradation & rupture

Matrix-metalloproteinase-driven degradation of the fibrous cap extracellular matrix, cap thinning and rupture exposing the thrombogenic lipid core.

79 molecules · 64 druggable · 0 with clinical trials

Canonical markers: MMP-9, MMP-2, PAPP-A, TIMP-1

Matrix metalloproteinase-9MMP9

MMP-9 degrades extracellular matrix in the atherosclerotic fibrous cap, promoting rupture and thrombotic exposure.

39 refsgeneticdruggable

Matrix Metalloproteinase-2MMP2

MMP-2 degrades the fibrous cap and myocardial ECM, mediating plaque rupture and post-infarction ventricular remodeling.

13 refsdruggable

Pregnancy-associated Plasma Protein APAPPA

PAPP-A is a metalloproteinase elevated in atherosclerotic plaques that degrades extracellular matrix, promoting cap rupture and thrombosis.

11 refsgeneticdruggable

Collagen Type I Alpha 1COL1A1

COL1A1 is the major fibrous-cap structural protein; its exposure upon rupture initiates platelet adhesion and thrombosis.

10 refsdruggable

Tissue inhibitor of metalloproteinases-1TIMP1

TIMP-1 inhibits MMP-driven fibrous-cap degradation and mediates ECM remodeling and cardiac fibrosis post-MI.

7 refsdruggable

Cathepsin DCTSD

Cathepsin D degrades extracellular-matrix proteins in atherosclerotic plaques and mediates macrophage apoptosis post-MI, influencing plaque stability and myocar

6 refsdruggable

Matrix metalloproteinase-3MMP3

MMP-3 degrades fibrous-cap collagen and proteoglycans, promoting plaque destabilization and rupture.

6 refsdruggable

ADAMTS7 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs 7)ADAMTS7

Matrix metalloproteinase promoting fibrous-cap degradation, arterial calcification, and endothelial dysfunction driving atherosclerotic MI.

5 refsdruggable

LumicanLUM

Lumican cross-links collagen fibrils in the fibrous cap, reinforcing structural integrity against rupture.

4 refsdruggable

BiglycanBGN

Biglycan reinforces fibrous-cap ECM architecture and locally inhibits thrombin to protect plaque stability.

3 refsdruggable

Cathepsin LCTSL

Cathepsin L is a lysosomal cysteine protease that degrades atherosclerotic plaque extracellular matrix and also contributes to cardiomyocyte proteolysis during

3 refsdruggable

cathepsin SCTSS

Cathepsin S is a macrophage lysosomal protease that degrades fibrous-cap extracellular matrix in atherosclerosis.

3 refsdruggable

Collagen Type III Alpha 1 ChainCOL3A1

COL3A1 is a structural collagen component of the fibrous cap; its remodeling/turnover marks plaque degradation and post-MI healing.

3 refsdruggable

Fibrinogen-Like Protein 1FGL1

FGL1 is released following plaque rupture and participates in inflammatory and hemostatic responses, potentially stabilizing or propagating the thrombus.

3 refsdruggable

Matrix metalloproteinase-1MMP1

Matrix metalloproteinase-1 degrades fibrous cap collagen and extracellular matrix, triggering atherosclerotic plaque rupture and thrombus exposure.

3 refsgeneticdruggable

Procollagen C-Endopeptidase EnhancerPCOLCE

PCOLCE promotes fibrous-cap collagen proteolysis and extracellular-matrix remodeling, facilitating plaque rupture and post-MI remodeling.

3 refsdruggable

proline

Proline metabolism, a marker of collagen turnover, may discriminate plaque erosion from rupture mechanisms in Type 1 MI pathogenesis.

3 refs

VersicanVCAN

Versican remodeling in the fibrous cap reduces structural integrity and promotes cap degradation.

3 refsdruggable

α-Smooth Muscle ActinACTA2

ACTA2 (α-SMA) marks myofibroblast activation and fibrotic remodeling of the atherosclerotic plaque and myocardium.

3 refs

ADAMTS4ADAMTS4

ADAMTS4 metalloprotease degrades versican and other proteoglycans in the atherosclerotic plaque extracellular matrix, promoting fibrous-cap thinning and remodel

2 refsdruggable

ALDH4A1ALDH4A1

ALDH4A1 autoimmunity marks atherosclerotic plaque instability and fibrous-cap erosion.

2 refsdruggable

Cathepsin BCTSB

Cathepsin B degrades collagen and elastin in the fibrous cap, promoting thinning and rupture in unstable plaques.

2 refsdruggable

ChymaseCMA1

Chymase from activated mast cells degrades fibrous-cap matrix proteins, contributing to cap thinning and rupture in destabilizing plaques.

2 refsgeneticdruggable

COL4A1COL4A1

COL4A1 maintains plaque stability through collagen IV production and supports smooth-muscle-cell survival; its remodeling marks post-MI fibrosis.

2 refsgeneticdruggable

COL4A2COL4A2

COL4A2 variants confer coronary artery disease susceptibility via effects on collagen IV-mediated plaque stabilization and fibrous-cap integrity.

2 refsgeneticdruggable

Collagen type I alpha-2 chainCOL1A2

COL1A2 is the predominant fibrillar collagen dysregulated in post-MI fibrotic remodeling.

2 refsdruggable

Collagen VI alpha-3COL6A3

COL6A3 maintains extracellular matrix integrity in the arterial wall and atherosclerotic plaque, supporting fibrous-cap resistance to degradation.

2 refsgeneticdruggable

Hyaluronic Acid

Hyaluronic acid is an ECM regulator whose elevated plasma levels reflect matrix turnover during atherosclerotic plaque destabilization and erosion.

2 refs

Interferon-Inducible T-Cell Alpha ChemoattractantCXCL11

I-TAC is elevated in ruptured atherosclerotic plaques, reflecting leukocyte recruitment and inflammatory destabilization of the fibrous cap.

2 refsdruggable

Matrix Metalloproteinase-12MMP12

MMP-12 mediates extracellular matrix degradation and infarct remodeling in MI.

2 refsdruggable

Plasminogen Activator, UrokinasePLAU

PLAU encodes urokinase, a serine protease that degrades fibrin and extracellular matrix, contributing to fibrous-cap rupture and thrombus formation.

2 refsgeneticdruggable

Thrombospondin-4THBS4

Thrombospondin-4 is an ECM protein dysregulated in atherosclerotic plaque progression and fibrous-cap remodeling.

2 refsdruggable

Tissue Inhibitor of Metalloproteinases 2TIMP2

TIMP2 suppresses matrix metalloproteinase activity, protecting fibrous-cap collagen from degradation.

2 refsdruggable

ADAM9ADAM9

ADAM9 proteolytic activity destabilizes the atherosclerotic plaque fibrous cap via matrix degradation, promoting rupture.

1 refsdruggable

ADAMTS1 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs 1)ADAMTS1

ADAMTS1 upregulation contributes to fibrous-cap degradation and atherosclerotic plaque rupture.

1 refsdruggable

Aggrecanase

Aggrecanase-mediated degradation of plaque extracellular matrix reduces fibrous cap integrity and increases rupture risk.

1 refs

Alpha-1 AntitrypsinSERPINA1

Alpha-1 antitrypsin inhibits neutrophil elastase and matrix metalloproteinases, protecting fibrous-cap integrity in atherosclerotic plaques.

1 refsdruggable

Amyloid-beta 1-40

Amyloid-beta 1-40 destabilizes atherosclerotic plaques by promoting matrix degradation, precipitating rupture and thrombosis.

1 refs

Bone Morphogenetic Protein 1BMP1

BMP1 regulates extracellular matrix remodeling and collagen degradation in atherosclerotic lesions.

1 refsdruggable

Calponin-2CNN2

CNN2 dysregulation alters smooth-muscle cell function and plaque structural integrity.

1 refsdruggable

Cartilage oligomeric matrix proteinCOMP

COMP participates in fibrous-cap matrix degradation and tissue remodeling following myocardial injury.

1 refsdruggable

Cathepsin

Cathepsin proteolysis of extracellular matrix proteins weakens the fibrous cap and promotes plaque rupture.

1 refs

Cathepsin ACTSA

CTSA (cathepsin A) degrades fibrous-cap matrix and contributes to plaque instability; targeting it may stabilize lesions post-MI.

1 refsdruggable

cathepsin KCTSK

Cathepsin K is a macrophage lysosomal protease elevated in atherosclerosis, contributing to fibrous-cap matrix degradation.

1 refsdruggable

Cathepsin XCTSX

Cathepsin X, a macrophage-derived protease, degrades fibrous-cap collagen and elastin, promoting plaque rupture in acute coronary syndromes.

1 refs

CFDP1CFDP1

CFDP1 regulates smooth-muscle cell function and may contribute to fibrous-cap maintenance and stability.

1 refs

Collagen type V alpha-2 chainCOL5A2

COL5A2 is a structural collagen involved in post-MI fibrotic cardiac remodeling.

1 refsdruggable

Collagen Type VI Alpha 1COL6A1

COL6A1 is a fibrous-cap collagen subject to degradation during plaque rupture.

1 refsdruggable

Collagen VI Alpha-2 ChainCOL6A2

COL6A2 expression and integrity in the plaque matrix reflect cap stability; reduced levels indicate erosion-prone remodeling.

1 refsdruggable

DecorinDCN

Decorin is a key ECM proteoglycan whose abundance and crosslinking state determine fibrous-cap mechanical integrity and rupture susceptibility.

1 refsdruggable

ElafinPI3

Serine-protease inhibitor that counterbalances matrix degradation during plaque destabilization and rupture.

1 refsdruggable

Extracellular Matrix Protein 1ECM1

ECM1 affects extracellular matrix integrity and vascular stability in SCAD.

1 refs1 omicsdruggable

Fetuin-BFETUB

Fetuin-B modulates protease activity and extracellular matrix remodeling affecting fibrous-cap stability and rupture susceptibility.

1 refsdruggable

GPNMBGPNMB

GPNMB regulates inflammation and extracellular matrix deposition post-MI, influencing fibrous cap stability and plaque remodeling.

1 refsdruggable

GZMBGZMB

Granzyme B from infiltrating cytotoxic lymphocytes degrades fibrous-cap collagen and is a plaque vulnerability driver in Type 1 MI.

1 refsdruggable

Kallikrein-6KLK6

Kallikrein protease contributes to matrix degradation and plaque instability preceding Type 1 MI.

1 refsdruggable

Laminin-1 (α1β1γ1)LAMA1

Basement-membrane component marking severe myocardial necrosis and ventricular remodeling in extensive infarction.

1 refsdruggable

Latent TGF-Beta Binding Protein 1LTBP1

LTBP1 sequesters latent TGF-β and stabilizes extracellular matrix, protecting the fibrous cap.

1 refsdruggable

LR11SORL1

Lipoprotein-receptor family member regulating smooth-muscle proliferation and cap composition.

1 refsdruggable

MAP1SMAP1S

MAP1S regulates smooth-muscle cell phenotype and may influence fibrous-cap stability in atherosclerosis.

1 refs

Matrix Metalloproteinase-25MMP25

MMP-25 drives fibrous cap degradation and post-infarct ventricular remodeling.

1 refsdruggable

Matrix Metalloproteinase-7MMP7

MMP-7 degrades fibrous-cap collagen and proteoglycans, promoting cap destabilization and rupture, and is elevated in CAD and MI patients.

1 refsgeneticdruggable

miR-221

miR-221 regulates vascular smooth-muscle proliferation and endothelial function relevant to plaque stability and stenosis severity.

1 refs

miR-222

miR-222 regulates vascular remodeling and endothelial function influencing plaque stability and coronary stenosis severity.

1 refs

miR-324-3p

miR-324-3p is dysregulated in plaque rupture, potentially regulating extracellular-matrix remodeling.

1 refs

miR-379

miR-379 suppresses vascular smooth muscle cell proliferation, influencing fibrous-cap integrity and atherosclerotic plaque stability.

1 refs

miR-744-3p

miR-744-3p is dysregulated in plaque rupture, potentially modulating matrix-degradation or inflammatory pathways.

1 refs

NidogenNID1

Nidogen maintains basement-membrane structure supporting fibrous-cap stability and endothelial barrier function.

1 refsdruggable

Proteinase 3PRTN3

Proteinase 3 released by activated neutrophils degrades fibrous-cap matrix proteins, promoting cap thinning and rupture.

1 refsdruggable

Proteoglycan 4PRG4

Proteoglycan 4 contributes to extracellular matrix organization and plaque structural stability.

1 refsdruggable

PRSS23PRSS23

PRSS23 is a trypsin-like serine protease; smoking-associated variants may affect fibrous-cap matrix turnover in AMI.

1 refsdruggable

RAB39ARAB39A

RAB39A dysregulation associates with atherosclerotic plaque rupture and acute coronary events in Type 1 MI.

1 refsdruggable

SPARC-Like Protein 1SPARCL1

SPARCL1 maintains vessel wall structural integrity; its dysregulation compromises fibrous-cap stability in Type 1 MI.

1 refsdruggable

Thrombospondin Type 1 Domain Containing 4THSD4

THSD4 supports structural integrity of connective tissue and aortic wall, reducing plaque rupture risk.

1 refsdruggable

TIMP metalloproteinase inhibitor 3TIMP3

TIMP3 inhibition of matrix metalloproteinases protects fibrous-cap integrity, preventing plaque rupture and thrombotic occlusion.

1 refsdruggable

Tissue Inhibitor of Metalloproteinases-4TIMP4

TIMP4 inhibits matrix metalloproteinase activity, protecting the fibrous cap from degradation and rupture.

1 refsdruggable

Transforming Growth Factor Beta Receptor IITGFBR2

TGFBR2 mediates TGF-β signaling controlling smooth-muscle proliferation and extracellular-matrix remodeling during fibrous-cap thinning.

1 refsdruggable

Trypsin

Trypsin degrades fibrous-cap collagen and elastin while activating protease-activated receptors that destabilize the plaque.

1 refs

Heat shock protein 47 (HSP47)SERPINH1

Stabilizes and matures interstitial collagen in plaque fibrous cap, reducing rupture risk.

geneticdruggable