# Novel molecular mechanisms of vascular smooth muscle cell-mediated large and small artery calcification

> **NIH NIH K01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $161,648

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal describes a 5-year training program for the development of an academic career in cardiovascular
research. Dr. Lino Cardenas will gain from the expertise of multiple investigators in an environment of over 100
faculty and will have access to a wide range of biomedical core facilities at MGH/HMS to aid in the successful
completion of the research program outlined in his application. Dr. Lino Cardenas's research program focuses
on the molecular mechanisms of vascular calcification, highly relevant to the pathogenesis of acute coronary
syndromes, atherosclerosis, and peripheral arterial disease. Growing evidence points towards autophagy, an
evolutionarily conserved process, as being protective during early atherosclerosis. However, autophagy can
become dysregulated with advanced atherosclerosis. In preliminary studies, Dr. Lino Cardenas has observed
that pharmacologic activation of the autophagy pathway reduces vascular calcification in Mgp-/- mice (mouse
model of spontaneous vascular calcification) and improves survival. The candidate proposes to define the
precise molecular mechanisms by which disruption of autophagy exacerbates vascular calcification with the
following two aims: In Aim 1, the candidate's first objective is to determine the role of vascular smooth muscle
cell (VSMC)-specific autophagy dysregulation on the development of vascular calcification and whether
modulation of autophagy may inhibit vascular calcification. Dr. Lino Cardenas will extend his preliminary findings
by combining RNA-seq, ChIP-seq and ATAC-seq technologies to define the effects of chromatin plasticity on the
autophagy pathway during vascular calcification. Dr. Lino Cardenas will study the therapeutic effect of a range
of autophagy modulators on VSMC phenotype and calcification in vitro and ex vivo. In Aim 2, the candidate will
determine whether pharmacologic or genetic activation of the autophagy pathway inhibits vascular calcification
in vivo using two different murine models of vascular calcification. Enhancing knowledge of novel molecular
mechanisms responsible for vascular calcification may hold important clinical implications and provide new
targets for the treatment of cardiovascular disease. The candidate aims to accomplish the following immediate
and long-term career goals: (1) To develop a broader understanding of the molecular mechanisms resulting in
vascular calcification. (2) To learn genomice-phenotype analyses using existing human genetic databases to
identify polymorphisms in autophagy initiation genes associated with vascular phenotypes. Additionally, Dr. Lino
Cardenas will learn advanced techniques in molecular biology and conditional gene deletion in multiple murine
models. (3) To develop under the guidance of his mentors and advisory committee the necessary skills of
directing a laboratory, fostering productive research collaborations and grant writing (4) To successfully apply
for R01 funding within 3 years...

## Key facts

- **NIH application ID:** 10507440
- **Project number:** 1K01HL164687-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Christian Lacks Lino Cardenas
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $161,648
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507440

## Citation

> US National Institutes of Health, RePORTER application 10507440, Novel molecular mechanisms of vascular smooth muscle cell-mediated large and small artery calcification (1K01HL164687-01). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10507440. Licensed CC0.

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