# Effects of miR-30c deficiency on plasma cholesterol and atherosclerosis

> **NIH NIH R01** · NEW YORK UNIVERSITY D/B/A NYU LONG ISLAND SCHOOL OF MEDICINE · 2020 · $269,548

## Abstract

High plasma cholesterol levels, a major risk factor for atherosclerosis, can be reduced by inhibiting lipoprotein
production; however, this is associated with steatosis. We showed that over expression of miR-30c lowers diet-
induced hypercholesterolemia and atherosclerosis in C57BL/6J wild type and Apoe−/− mice. Conversely,
inhibition of hepatic miR-30c increased plasma cholesterol and atherosclerosis. Based on these exciting
published data, we hypothesize that endogenous miR-30c is an important regulator of lipid metabolism and
that miR-30c deficiency will enhance plasma and tissue lipids, plasma cytokines and atherosclerosis. We will
evaluate this hypothesis using double knockout (DKO) Mir30c1−/−;Mir30c2−/− and triple KO
Mir30c1−/−;Mir30c2−/−;Apoe−/− mice fed chow and western diets with and without fructose. Next, we will establish
the direct and specific role of miR-30c in the development of hypercholesterolemia and early and advanced
atherosclerotic lesions by re-expressing miR-30c in the liver and spleen of these knockout mice using different
strategies. Further, using similar knockout and re-expression strategies, we will elucidate physiological
mechanisms (hepatic lipoprotein production, de novo lipogenesis and macrophage cytokine production)
involved in the regulation of hypercholesterolemia, steatosis, inflammatory response and atherosclerosis by
miR-30c. Moreover, we will evaluate the molecular hypothesis that miR-30c deficiency deregulates MTP,
LPGAT1 and ELOVL5 in hepatocytes; and IKKα in macrophages to cause hypercholesterolemia, steatosis,
and pro-inflammatory cytokine production. These studies will establish the importance of endogenous miR-30c
in the regulation of plasma and tissue lipids and cytokine production, and will elucidate physiological,
biochemical and molecular mechanisms involved in the regulation of various biological pathways by miR-30c.
At the end, these studies will furnish novel information concerning the protective role of whole body as well as
liver- and macrophage-specific miR-30c against diet-induced metabolic disorders.

## Key facts

- **NIH application ID:** 10424970
- **Project number:** 6R01HL137202-05
- **Recipient organization:** NEW YORK UNIVERSITY D/B/A NYU LONG ISLAND SCHOOL OF MEDICINE
- **Principal Investigator:** M Mahmood Hussain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $269,548
- **Award type:** 6
- **Project period:** 2017-06-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424970

## Citation

> US National Institutes of Health, RePORTER application 10424970, Effects of miR-30c deficiency on plasma cholesterol and atherosclerosis (6R01HL137202-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10424970. Licensed CC0.

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